Iordanis E. Evangelou

Relationship of Cortical Atrophy to Fatigue in Patients With Multiple Sclerosis

BACKGROUND Fatigue is a common and disabling symptom of multiple sclerosis (MS). Previous studies reported that damage of the corticostriatothalamocortical circuit is critical in its occurrence. OBJECTIVE To investigate the relationship between fatigue in MS and regional cortical and subcortical gray matter atrophy. DESIGN Case-control study. SETTING National Institutes of Health. PARTICIPANTS Twenty-four patients with MS and 24 matched healthy volunteers who underwent 3.0-T magnetic resonance imaging and evaluations of fatigue (Modified Fatigue Impact Scale) and depression (Center for Epidemiologic Studies Depression Scale). MAIN OUTCOME MEASURES Relationship between thalamic and basal ganglia volume, cortical thickness of frontal and parietal lobes, and, in patients, T2 lesion volume and normal-appearing white matter volume and the extent of fatigue. RESULTS Patients were more fatigued than healthy volunteers (P = .04), while controlling for the effect of depression. Modified Fatigue Impact Scale score correlated with cortical thickness of the parietal lobe (r = -0.50, P = .01), explaining 25% of its variance. The posterior parietal cortex was the only parietal area significantly associated with the Modified Fatigue Impact Scale scores. CONCLUSIONS Cortical atrophy of the parietal lobe had the strongest relationship with fatigue. Given the implications of the posterior parietal cortex in motor planning and integration of information from different sources, our preliminary results suggest that dysfunctions in higher-order aspects of motor control may have a role in determining fatigue in MS.

Evolution of the blood–brain barrier in newly forming multiple sclerosis lesions

Multiple sclerosis (MS) lesions develop around small, inflamed veins. New lesions enhance with gadolinium on magnetic resonance imaging (MRI), reflecting disruption of the blood–brain barrier (BBB). Single time point results from pathology and standard MRI cannot capture the spatiotemporal expansion of lesions. We investigated the development and expansion of new MS lesions, focusing on the dynamics of BBB permeability.

Thalamic Involvement and Its Impact on Clinical Disability in Patients with Multiple Sclerosis: A Diffusion Tensor Imaging Study at 3T

BACKGROUND AND PURPOSE: Several studies suggest that grey matter involvement may play a role in multiple sclerosis (MS) pathology. Diffusion tensor imaging (DTI) at 3T was used to investigate the presence of damage to the normal-appearing thalamus in MS and its relationship with disability. MATERIALS AND METHODS: Twenty-four patients with relapsing-remitting (RR, n = 13, age = 41.7 ± 6.1, Expanded Disability Status Scale [EDSS] score = 2.2 ± 1.2) and secondary-progressive (n = 11, age = 46.9 ± 9.6, EDSS = 5.9 ± 1.0) MS and 24 age- and sex-matched healthy volunteers were studied. Fractional anisotropy (FA) and mean diffusivity (MD) were measured in regions of interest of normal-appearing thalamus. We examined group differences in MD and FA and correlations between DTI-derived metrics and clinical or imaging measures of disease. RESULTS: Patients with MS had higher thalamic FA (P < .0001) and MD (P = .035) than volunteers. MD values correlated with the Paced Auditory Serial Addition Task (r = −0.43, P = .034) and motor EDSS (r = 0.47, P = .021) scores. In patients with RRMS, MD values correlated with global EDSS (r = 0.75, P = .003) and motor EDSS (r = 0.68, P = .010). Correlations were found between MD values and T1 and T2 lesion load (r = 0.58, P < .05) and brain parenchymal fraction (r = −0.46, P < .05). CONCLUSIONS: DTI was able to detect abnormalities in normal-appearing thalamus of patients with MS. The strength of association between thalamic DTI measures and functional impairment was in the same range as those seen with standard MR imaging disease measures. The assessment of the integrity of the thalamus with DTI is a promising metric as a marker of disease for future studies.

Impaired functional but preserved structural connectivity in limbic white matter tracts in youth with conduct disorder or oppositional defiant disorder plus psychopathic traits

Youths with conduct disorder or oppositional defiant disorder and psychopathic traits (CD/ODD+PT) are at high risk of adult antisocial behavior and psychopathy. Neuroimaging studies demonstrate functional abnormalities in orbitofrontal cortex and the amygdala in both youths and adults with psychopathic traits. Diffusion tensor imaging in psychopathic adults demonstrates disrupted structural connectivity between these regions (uncinate fasiculus). The current study examined whether functional neural abnormalities present in youths with CD/ODD+PT are associated with similar white matter abnormalities. Youths with CD/ODD+PT and comparison participants completed 3.0 T diffusion tensor scans and functional magnetic resonance imaging scans. Diffusion tensor imaging did not reveal disruption in structural connections within the uncinate fasiculus or other white matter tracts in youths with CD/ODD+PT, despite the demonstration of disrupted amygdala-prefrontal functional connectivity in these youths. These results suggest that disrupted amygdala-frontal white matter connectivity as measured by fractional anisotropy is less sensitive than imaging measurements of functional perturbations in youths with psychopathic traits. If white matter tracts are intact in youths with this disorder, childhood may provide a critical window for intervention and treatment, before significant structural brain abnormalities solidify.

White matter tract integrity and developmental outcome in newborn infants with hypoxic-ischemic encephalopathy treated with hypothermia.

To determine whether corpus callosum (CC) and corticospinal tract (CST) diffusion tensor imaging (DTI) measures relate to developmental outcome in encephalopathic newborn infants after therapeutic hypothermia.

Frequency of Hospitalizations for Pain and Association With Altered Brain Network Connectivity in Sickle Cell Disease

UNLABELLED Sickle cell disease (SCD) is a hemoglobinopathy that affects more than 100,000 individuals in the United States. The disease is characterized by the presence of sickle hemoglobin and recurrent episodes of pain. Some individuals with SCD experience frequent hospitalizations and a high burden of pain. The role of central mechanisms in SCD pain has not been explored. Twenty-five adolescents and young adults with SCD underwent functional magnetic resonance imaging. Participants were stratified into groups with high pain or low pain based on the number of hospitalizations for pain in the preceding 12 months. Resting state functional connectivity was analyzed using seed-based and dual regression independent component analysis. Intrinsic brain connectivity was compared between the high pain and low pain groups, and association with fetal hemoglobin, a known modifier of SCD, was explored. Patients in the high pain group displayed an excess of pronociceptive connectivity such as between anterior cingulate and default mode network structures, such as the precuneus, whereas patients in the low pain group showed more connectivity to antinociceptive structures such as the perigenual and subgenual cingulate. Although a similar proportion of patients in both groups reported that they were on hydroxyurea, the fetal hemoglobin levels were significantly higher in the low pain group and were associated with greater connectivity to antinociceptive structures. These findings support the role of central mechanisms in SCD pain. Intrinsic brain connectivity should be explored as a complementary and objective outcome measure in SCD pain research. PERSPECTIVE Altered connectivity patterns associated with high pain experience in patients with sickle cell disease suggest a possible role of central mechanisms in sickle cell pain. Resting state brain connectivity studies should be explored as an effective methodology to investigate pain in SCD.

Impaired Global and Regional Cerebral Perfusion in Newborns with Complex Congenital Heart Disease

OBJECTIVE To compare global and regional cerebral perfusion in newborns with congenital heart disease (CHD) and healthy controls using arterial spin labeling (ASL) magnetic resonance imaging (MRI) prior to open heart surgery. STUDY DESIGN We performed brain MRIs in 101 newborns (58 controls, 43 CHD) using 3-dimensional fast spin echo pseudo-continuous ASL. Cerebral blood flow (CBF) ASL images were linearly coregistered to T2-weighted images for anatomic delineation and selection of regions-of-interest. Anatomic regions included frontal white matter (FWM), occipital white matter (OWM), thalami, and basal ganglia (BG). RESULTS Newborns with single ventricle CHD demonstrated significantly lower global (P = .044) and regional BG (P = .025) CBF compared with controls. Mean regional CBF in the thalami in cyanotic newborns with CHD was lower compared with controls (P = .004). Mean regional CBF in thalami (P = .02), BG (P = .01), and OWM (P = .03) among newborns with cyanotic CHD was lower than those with acyanotic CHD. Newborns with CHD ventilated prior to MRI had increased global (P = .016) and OWM (P = .013) CBF compared with those not ventilated. CONCLUSIONS Newborns with uncorrected cyanotic or single ventricle CHD show disturbances in cerebral perfusion compared to healthy controls using ASL. Cardiac physiology and preoperative hemodynamic compromise play an important role in preoperative alterations in global and regional cerebral perfusion. Our data suggest that ASL may be useful for studying cerebral perfusion in newborns at high risk for cerebral ischemia, such as those with complex CHD.

Functional properties of resting state networks in healthy full-term newborns.

Objective, early, and non-invasive assessment of brain function in high-risk newborns is critical to initiate timely interventions and to minimize long-term neurodevelopmental disabilities. A prerequisite to identifying deviations from normal, however, is the availability of baseline measures of brain function derived from healthy, full-term newborns. Recent advances in functional MRI combined with graph theoretic techniques may provide important, currently unavailable, quantitative markers of normal neurodevelopment. In the current study, we describe important properties of resting state networks in 60 healthy, full-term, unsedated newborns. The neonate brain exhibited an efficient and economical small world topology: densely connected nearby regions, sparse, but well integrated, distant connections, a small world index greater than 1, and global/local efficiency greater than network cost. These networks showed a heavy-tailed degree distribution, suggesting the presence of regions that are more richly connected to others (‘hubs’). These hubs, identified using degree and betweenness centrality measures, show a more mature hub organization than previously reported. Targeted attacks on hubs show that neonate networks are more resilient than simulated scale-free networks. Networks fragmented faster and global efficiency decreased faster when betweenness, as opposed to degree, hubs were attacked suggesting a more influential role of betweenness hub in the neonate network.

Quality and Quantity of Diffuse and Focal White Matter Disease and Cognitive Disability of Patients with Multiple Sclerosis

Using high‐field magnetic resonance imaging (MRI), we investigated the relationships between white matter (WM) lesion volume (LV), normal‐appearing WM (NAWM) normalized volume, WM‐lesion and NAWM magnetization transfer ratios (MTRs), brain parenchyma fraction (BPF), and cognitive impairment (CI) in multiple sclerosis (MS).

Complex Trajectories of Brain Development in the Healthy Human Fetus

Abstract This study characterizes global and hemispheric brain growth in healthy human fetuses during the second half of pregnancy using three‐dimensional MRI techniques. We studied 166 healthy fetuses that underwent MRI between 18 and 39 completed weeks gestation. We created three‐dimensional high‐resolution reconstructions of the brain and calculated volumes for left and right cortical gray matter (CGM), fetal white matter (FWM), deep subcortical structures (DSS), and the cerebellum. We calculated the rate of growth for each tissue class according to gestational age and described patterns of hemispheric growth. Each brain region demonstrated major increases in volume during the second half of gestation, the most pronounced being the cerebellum (34‐fold), followed by FWM (22‐fold), CGM (21‐fold), and DSS (10‐fold). The left cerebellar hemisphere, CGM, and DSS had larger volumes early in gestation, but these equalized by term. It has been increasingly recognized that brain asymmetry evolves throughout the human life span. Advanced quantitative MRI provides noninvasive measurements of early structural asymmetry between the left and right fetal brain that may inform functional and behavioral laterality differences seen in children and young adulthood.