Complex Trajectories of Brain Development in the Healthy Human Fetus.

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.

Robust preprocessing for stimulus-based functional MRI of the moving fetus.

Fetal motion manifests as signal degradation and image artifact in the acquired time series of blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) studies. We present a robust preprocessing pipeline to specifically address fetal and placental motion-induced artifacts in stimulus-based fMRI with slowly cycled block design in the living fetus. In the proposed pipeline, motion correction is optimized to the experimental paradigm, and it is performed separately in each phase as well as in each region of interest (ROI), recognizing that each phase and organ experiences different types of motion. To obtain the averaged BOLD signals for each ROI, both misaligned volumes and noisy voxels are automatically detected and excluded, and the missing data are then imputed by statistical estimation based on local polynomial smoothing. Our experimental results demonstrate that the proposed pipeline was effective in mitigating the motion-induced artifacts in stimulus-based fMRI data of the fetal brain and placenta.

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.

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.

Neonatal neurobehavior after therapeutic hypothermia for hypoxic ischemic encephalopathy.

BACKGROUND: Perinatal hypoxic ischemic encephalopathy (HIE) is a major cause of neurodevelopmental impairment including cerebral palsy and intellectual disability. Brain magnetic resonance imaging is the gold standard for acute assessment of cerebral injury in HIE. Limited data are available regarding the significance of clinically manifested neurobehavioral impairments in the neonatal period. AIM: To evaluate brain structure-function relationships in newborns with HIE using diffusion tensor imaging (DTI) and the NICU Network Neurobehavioral Scale (NNNS). STUDY DESIGN: Prospective observational study with secondary longitudinal component. SUBJECTS: Forty-five newborns (62% male) with HIE referred for therapeutic hypothermia who underwent MRI and neurobehavioral assessment prior to discharge. OUTCOME MEASURES: DTI was performed at median age of 8 days (range 5-16) and NNNS at median 12 days of life (range 5-20, postmenstrual age 40±2 weeks). Developmental assessment with the Bayley Scales of Infant Development-II was performed at median age of 21.6 months (range 20.8-30.6). RESULTS: Significant associations were observed between DTI corticospinal tract integrity and NNNS neuromotor performance in HIE newborns. Neonatal neuromotor performance was also related to later early childhood motor outcomes. CONCLUSIONS: NNNS performed after therapeutic hypothermia in newborns with HIE can identify neuromotor abnormalities that are related to microstructural brain injury in the corticospinal tract and later motor outcomes in early childhood. These data support the NNNS as a valid early functional assessment of perinatal brain injury.

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.

3-D volumetric MRI evaluation of the placenta in fetuses with complex congenital heart disease.

INTRODUCTION: Placental insufficiency remains a common cause of perinatal mortality and neurodevelopmental morbidity. Congenital heart disease (CHD) in the fetus and its relationship to placental function is unknown. This study explores placental health and its relationship to neonatal outcomes by comparing placental volumes in healthy pregnancies and pregnancies complicated by CHD using in vivo three-dimensional MRI studies. METHODS: In a prospective observational study, pregnant women greater than 18 weeks gestation with normal pregnancies or pregnancies complicated by CHD were recruited and underwent fetal MR imaging. The placenta was manually outlined and the volume was calculated in cm(3). Brain volume was also calculated and clinical data were also collected. Relationships, including interactive effects, between placental and fetal growth, including brain growth, were evaluated using longitudinal multiple linear regression analysis. RESULTS: 135 women underwent fetal MRI between 18 and 39 weeks gestation (mean 31.6 ± 4.4). Placental volume increased exponentially with gestational age (p = 0.041). Placental volume was positively associated with birth weight (p < 0.001) and increased more steeply with birth weight in CHD-affected fetuses (p = 0.046). Total brain and cerebral volumes were smaller in the CHD group (p < 0.001), but brainstem volume (p < 0.001) was larger. Placental volumes were not associated with brain volumes. DISCUSSION: Impaired placental growth in CHD is associated with gestational age and birth weight at delivery. Abnormalities in placental development may contribute to the significant morbidity in this high-risk population. Assessment of placental volume by MRI allows for in vivo assessments of placental development.

Robust motion correction and outlier rejection of in vivo functional MR images of the fetal brain and placenta during maternal hyperoxia.

Subject motion is a major challenge in functional magnetic resonance imaging studies (fMRI) of the fetal brain and placenta during maternal hyperoxia. We propose a motion correction and volume outlier rejection method for the correction of severe motion artifacts in both fetal brain and placenta. The method is optimized to the experimental design by processing different phases of acquisition separately. It also automatically excludes high-motion volumes and all the missing data are regressed from ROI-averaged signals. The results demonstrate that the proposed method is effective in enhancing motion correction in fetal fMRI without large data loss, compared to traditional motion correction methods.

Diffuse and focal corticospinal tract disease and its impact on patient disability in multiple sclerosis.

BACKGROUND AND PURPOSE: We investigated the impact of focal and diffuse corticospinal tracts damage on sensory-motor disability in multiple sclerosis (MS) patients. METHODS: Twenty-five MS patients underwent 3.0 Tesla (3T) magnetic resonance imaging with diffusion tensor imaging (DTI). The Expanded Disability Status Scale (EDSS) and the Timed 25-Foot Walk test (T25FW) quantified patient physical disability. Fractional anisotropy (FA) and mean diffusivity (MD) of the corticospinal tracts, whole brain and corticospinal tracts lesion volume were also computed. Spearman rank correlation analyses measured the associations between DTI-derived metrics and other measures of disease. Partial correlation analyses between DTI and disability measures were performed and corrected for lesion volumes as appropriate. RESULTS: Significant associations were seen between FA of the corticospinal tracts and EDSS (r = -.500, P = .0011), motor-EDSS (r = -.519, P = .008), and T25WF (r = -.637, P = .001) scores and MD of the corticospinal tracts and motor-EDSS (r = .469, P = .018) and T25WF (r = .428, P = .033) scores. When correcting for lesion volumes, only the association between FA of the corticospinal tracts and EDSS (r ≤ -.516, p ≤ .01) or motor-EDSS score (r ≤ -.516, p ≤ .01) persisted. CONCLUSIONS: DTI at 3T shows that the impact of diffuse corticospinal tracts disease on sensory-motor disability is greatly mediated by focal lesions in MS.

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

AIM: 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. METHOD: Encephalopathic newborn infants enrolled in a longitudinal study underwent DTI after hypothermia. Parametric maps were generated for fractional anisotropy, mean, radial, and axial diffusivity. CC and CST were segmented by DTI-based tractography. Multiple regression models were used to examine the association of DTI measures with Bayley-II Mental (MDI) and Psychomotor Developmental Index (PDI) at 15 months and 21 months of age. RESULTS: Fifty-two infants (males n=32, females n=20) underwent DTI at median age of 8 days. Two were excluded because of poor magnetic resonance imaging quality. Outcomes were assessed in 42/50 (84%) children at 15 months and 35/50 (70%) at 21 months. Lower CC and CST fractional anisotropy were associated with lower MDI and PDI respectively, even after controlling for gestational age, birth weight, sex, and socio-economic status. There was also a direct relationship between CC axial diffusivity and MDI, while CST radial diffusivity was inversely related to PDI. INTERPRETATION: In encephalopathic newborn infants, impaired microstructural organization of the CC and CST predicts poorer cognitive and motor performance respectively. Tractography provides a reliable method for early assessment of perinatal brain injury.

HTLV-I-associated myelopathy/tropical spastic paraparesis: semiautomatic quantification of spinal cord atrophy from 3-dimensional MR images.

BACKGROUND: Human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a disabling neurological disorder characterized by inflammatory changes in the spinal cord. We used a semiautomatic technique to quantify spinal cord volume from 3-dimensional MR images of patients with HAM/TSP. METHODS: Five patients and 5 matched healthy volunteers (HVs) underwent MRI of the cervical and thoracic spinal cord at 1.5 T. Quantification of the spinal cord volume was obtained from 3-dimensional MR images using a semiautomatic technique based on level sets. An unpaired t-test was used to assess statistical significance. RESULTS: Significant differences were found between mean spinal cord volume of HVs and HAM/TSP patients. The thoracic spinal cord volume was 14,050 ± 981 mm(3) for HVs and 8,774 ± 2,218 mm(3) for HAM/TSP patients (P = .0079), a reduction of 38%. The cervical spinal cord volume was 9,721 ± 797 mm(3) for HVs and 6,589 ± 897 mm(3) for HAM/TSP patients (P = .0079), a reduction of 32%. These results suggest that atrophy is evident throughout the spinal cord not routinely quantified. CONCLUSIONS: Semiautomatic spinal cord volume quantification is a sensitive technique for quantifying the extent of spinal cord involvement in HAM/TSP.

Optimized methodology for neonatal diffusion tensor imaging processing and study-specific template construction.

Diffusion tensor imaging (DTI) has been widely used to study cerebral white matter microstructure in vivo. There is a plethora of open source tools available to perform pre-processing, analysis and template or atlas construction, however very few have been optimized for use with neonatal DTI data. Here we present a fully automated modular pipeline optimized for neonatal DTI data and the construction of study-specific tensor templates. We compare our methodology to an existing one. It is anticipated that the construction of population or study-specific templates will facilitate better group comparisons of neonatal populations both in health and disease.

Brain volume and neurobehavior in newborns with complex congenital heart defects.

OBJECTIVE: To investigate the relationship between tissue-specific alterations in brain volume and neurobehavioral status in newborns with complex congenital heart defects preoperatively. STUDY DESIGN: Three-dimensional volumetric magnetic resonance imaging was used to calculate tissue-specific brain volumes and a standardized neurobehavioral assessment was performed to assess neurobehavioral status in 35 full-term newborns admitted to the hospital before cardiopulmonary bypass surgery. Multiple linear regression models were performed to evaluate relationships between neurobehavioral status and brain volumes. RESULTS: Reduced subcortical gray matter (SCGM) volume and increased cerebrospinal fluid (CSF) volume were associated with poor behavioral state regulation (SCGM, P = .04; CSF, P = .007) and poor visual orienting (CSF, P = .003). In cyanotic newborns, reduced SCGM was associated with higher overall abnormal scores on the assessment (P = .001) and poor behavioral state regulation (P = .04), and increased CSF volume was associated with poor behavioral state regulation (P = .02), and poor visual orienting (P = .02). Conversely, acyanotic newborns showed associations between reduced cerebellar volume and poor behavioral state regulation (P = .03). CONCLUSION: Abnormal neurobehavior is associated with impaired volumetric brain growth before open heart surgery in infants with complex congenital heart defects. This study highlights a need for routine preoperative screening and early intervention to improve neurodevelopmental outcomes.

Cognitive impairment and its relation to imaging measures in multiple sclerosis: a study using a computerized battery.

BACKGROUND AND PURPOSE: Cognitive impairment (CI) is an important component of multiple sclerosis (MS) disability. A complex biological interplay between white matter (WM) and gray matter (GM) disease likely sustains CI. This study aims to address this issue by exploring the association between the extent of normal WM and GM disease and CI. METHODS: Cognitive function of 24 MS patients and 24 healthy volunteers (HVs) was studied using the Automated Neuropsychological Assessment Metrics (ANAM) battery. WM focal lesions and normal appearing WM (NAWM) volume in patients, cortical thickness (CTh) and deep GM structure volumes in both patients and HVs were measured by high field strength (3.0-Tesla; 3T) imaging. RESULTS: An analysis of covariance showed that patients performed worse than HVs on Code Substitution Delayed Memory (P = .04) and Procedural Reaction Time (P = .05) indicative of reduced performance in memory, cognitive flexibility, and processing speed. A summary score (Index of Cognitive Efficiency) indicating global test battery performance was also lower for the patient group (P = .04). Significant associations, as determined by the Spearman rank correlation tests, were noted between each of these 3 cognitive scores and measures of NAWM volume [CDD-TP1(r = .609; P = .0035), PRO-TP1 (r = .456; P = .029) and ICE (r = .489; P = .0129)], CTh (r = .5; P ≤ .05) and volume of subcortical normal appearing GM (NAGM) structures (r = .4; P≤ .04), but not WM lesions. CONCLUSIONS: Both NAWM and NAGM volumes are related to CI in MS. The results highlight once again the urgent need to develop pharmacological strategies protecting patients from widespread neurodegeneration as possible preventive strategies of CI development.

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.

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

OBJECTIVE: 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. METHODS: We performed dynamic contrast-enhanced (DCE) MRI in relapsing-remitting MS. We obtained data over 65 minutes, during and after gadolinium injection. We labeled spatiotemporal enhancement dynamics as centrifugal when initially central enhancement expanded outward and centripetal when initially peripheral enhancement gradually filled the center. RESULTS: We detected 34 enhancing lesions in 200 DCE-MRI scans. In 65%, enhancement first appeared as a closed ring; in 18%, as a nodule; and in 18%, as an open ring. Lesions with initially nodular enhancement were smaller than those initially enhancing as rings (p < 0.0001). All initially nodular lesions enhanced centrifugally, whereas initially ringlike lesions enhanced centripetally, becoming nodular if small (82%) or nearly nodular if larger (18%). Open-ring lesions were periventricular or juxtacortical and enhanced centripetally. Centrifugally enhancing lesions evolved into centripetally enhancing lesions over several days. INTERPRETATION: The rapid change of enhancement dynamics from centrifugal to centripetal reflects the outward growth of MS lesions around their central vein and suggests that factors mediating lesion growth and tissue repair derive from different locations at different times. We propose a model of new lesion growth that unites our imaging observations with existing pathology data.

Translocator protein PET imaging for glial activation in multiple sclerosis.

Glial activation in the setting of central nervous system inflammation is a key feature of the multiple sclerosis (MS) pathology. Monitoring glial activation in subjects with MS, therefore, has the potential to be informative with respect to disease activity. The translocator protein 18 kDa (TSPO) is a promising biomarker of glial activation that can be imaged by positron emission tomography (PET). To characterize the in vivo TSPO expression in MS, we analyzed brain PET scans in subjects with MS and healthy volunteers in an observational study using [(11)C]PBR28, a newly developed translocator protein-specific radioligand. The [(11)C]PBR28 PET showed altered compartmental distribution of TSPO in the MS brain compared to healthy volunteers (p = 0.019). Focal increases in [(11)C]PBR28 binding corresponded to areas of active inflammation as evidenced by significantly greater binding in regions of gadolinium contrast enhancement compared to contralateral normal-appearing white matter (p = 0.0039). Furthermore, increase in [(11)C]PBR28 binding preceded the appearance of contrast enhancement on magnetic resonance imaging in some lesions, suggesting a role for early glial activation in MS lesion formation. Global [(11)C]PBR28 binding showed correlation with disease duration (p = 0.041), but not with measures of clinical disability. These results further define TSPO as an informative marker of glial activation in MS.

Quality and quantity of diffuse and focal white matter disease and cognitive disability of patients with multiple sclerosis.

BACKGROUND AND PURPOSE: 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). METHODS: Twenty-four patients and 24 healthy volunteers (age, sex, and years of education-matched) underwent a 3.0 Tesla (3T) scan and evaluation of depression, fatigue, and CI using the Minimal Assessment of Cognitive Function in MS (MACFIMS) battery. RESULTS: In this clinically relatively well-preserved cohort of patients (median score on the Expanded Disability Status Scale=1.5), CI was detected on Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-II (CVLT-II), and Controlled Oral Word Association Test. MT data were available in 19 pairs on whom correlation analyses were performed. Associations were seen between SDMT and normalized NAWM volume (P=.034, r=.502), CVLT-II long delay and normalized NAWM volume (P=.012, r=.563), WM-LV (P=.024, r=.514), and BPF (P=.002, r=.666). CONCLUSIONS: The use of 3T MRI in a sample of clinically stable MS patients shows the importance of WM disease in hampering processing speed and word retrieval.

Template-based B1 inhomogeneity correction in 3T MRI brain studies.

Low noise, high resolution, fast and accurate T1 maps from MRI images of the brain can be performed using a dual flip angle method. However, B1 field inhomogeneity, which is particularly problematic at high field strengths (e.g., 3T), limits the ability of the scanner to deliver the prescribed flip angle, introducing errors into the T1 maps that limit the accuracy of quantitative analyses based on those maps. A dual repetition time method was used for acquiring a B1 map to correct that inhomogeneity. Additional inaccuracies due to misregistration of the acquired T1-weighted images were corrected by rigid registration, and the effects of misalignment on the T1 maps were compared to those of B1 inhomogeneity in 19 normal subjects. However, since B1 map acquisition takes up precious scanning time and most retrospective studies do not have B1 map, we designed a template-based correction strategy. B1 maps from different subjects were aligned using a twelve-parameter affine registration. Recomputed T1 maps showed an important improvement with respect to the noncorrected maps: histograms of all corrected maps exhibited two peaks corresponding to white and gray matter tissues, while unimodal histograms were observed in all uncorrected maps because of the inhomogeneity. A method to detect the best nonsubject-specific B1 correction based on a set of features was designed. The optimum set of weighting factors for those features was computed. The best available B1 correction was detected in almost all subjects while corrections comparable to the T1 map corrected using the B1 map from the same subject were detected in the others.

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.