Insight into brain sex differences of typically developed infants and brain pathologies: A systematic review.

The continually advancing landscape of neuroscientific and imaging research has broadened our comprehension of sex differences encoded in the human brain, expanding from the hypothalamus and sexual behaviour to encompass the entire brain, including its diverse lobes, structures, and functions. However, less is known about sex differences in the brains of neonates and infants, despite their relevance to various sex-linked diseases that develop early in life. In this review, we provide a synopsis of the literature evidence on sex differences in the brains of neonates and infants at the morphological, structural and network levels. We also briefly overview the present evidence on the sex bias in some brain disorders affecting infants and neonates.

Poststroke apathy: Major role of cognitive, depressive and neurological disorders over imaging determinants.

Apathy occurs in approximately one third of people after stroke. Despite its frequency and functional consequences, the determinants of apathy have only been partially defined. The major difficulty lies in disentangling the reduction in activity due to apathy itself from those secondary to comorbidities, such as depression, sensorimotor deficits, and cognitive impairment. Here, we aimed to examine the prevalence of apathy, identify confounding sources of hypoactivity, and define its neuroimaging determinants using multivariate voxel lesion symptom-mapping (mVLSM) analyses. We assessed apathy in a subgroup (n = 325, mean age: 63.8 ± 10.5 years, 91.1% ischemic stroke) of the GRECogVASC cohort using the validated Behavioral Dysexecutive Syndrome Inventory, interpreted using GREFEX criteria, as well as confounding factors (depression, anxiety, severity of the neurological deficit, and gait disorders). mVLSM analysis was used to define neuroimaging determinants and was repeated after controlling for confounding factors. Apathy was present for 120 patients (36.9%, 95% CI: 31.7-42.2). Stepwise linear regression identified three factors associated with apathy: depressive symptoms (R2 = .3, p = .0001), cognitive impairment (R2 = .015, p = .02), and neurological deficit (R2 = .110, p = .0001). Accordingly, only 9 (7.5%) patients had apathy without a confounding factor, i.e., isolated apathy. In conventional VLSM analysis, apathy was associated with a large number of subcortical lesions that were no longer considered after controlling for confounding factors. Strategic site analysis identified five regions associated with isolated apathy: the F3 orbitalis pars, left amygdala, left thalamus, left pallidum, and mesencephalon. mVLSM analysis identified four strategic sites associated with apathy: the right corticospinal tract (R2 = .11; p = .0001), left frontostriatal tract (R2 = .11; p = .0001), left thalamus (R2 = .04; p = .0001), and left amygdala (R2 = .01; p = .013). These regions remained significant after controlling for confounding factors but explained a lower amount of variance. These findings indicate that poststroke apathy is more strongly associated with depression, neurological deficit, and cognitive impairment than with stroke lesions locations, at least using VLSM analysis.

Poststroke action slowing: Motor and attentional impairments and their imaging determinants. Evidence from lesion-symptom mapping, disconnection and fMRI activation studies.

BACKGROUND AND OBJECTIVES: Although action slowing is the main cognitive impairment in stroke survivors, its mechanisms and determinants are still poorly understood. The objectives of the present study were to determine the mechanisms of post-stroke action slowing (using validated, highly specific simple reaction time (SRT) and tapping tests) and identify its imaging determinants (using multivariate lesion-symptom mapping (mLSM)). METHODS: Action speed in the GRECogVASC cohort was assessed using finger tapping and SRT tests performed with both hands and analyzed using previously validated indices. Imaging determinants were identified using validated mLSM analyses and disconnection analysis and compared to those of an fMRI activation meta-analytic database. RESULTS: Both the tapping time and SRT were 10.7% slower for the 394 patients (p = 0.0001) than for the 786 controls, without a group × test interaction (p = 0.2). The intra-individual distribution curve was characterized by a rightward shift with an unaltered attentional peak. The mLSM analyses showed tapping to be associated with lesions in the frontostriatal tract (p = 0.0007). The SRT was associated with lesions in the frontostriatal tract (p = 0.04) and the orbital part of F3 (p = 0.0001). The SRT-tapping index was associated with lesions in the orbital part of F3 (p = 0.0001). All lesions were located in the right hemisphere only and were responsible for the disconnection of several structures involved in motor preparation, initiation, and speed. A comparison with fMRI activation meta-analytic data highlighted mostly the same regions, including the orbital part of F3, the ventral and dorsal parts of F1, and the premotor and cingulate regions in the right hemisphere. DISCUSSION: Our results confirm the marked impairment of action speed in stroke and show that the primary mechanism is motor slowing and that it is related to lesions in the right frontostriatal tract. A deficit in sustained alertness accounted for action slowing in the subgroup with lesions in the right orbital part of F3. Our SRT and mLSM results were in accordance with the fMRI activation data. Thus, stroke induces slowing in the broad network associated with SRT tasks by disrupting the frontostriatal tract and, to a lesser extent, other sites involved in attention.

Clinical and Imaging Determinants of Neurocognitive Disorders in Post-Acute COVID-19 Patients with Cognitive Complaints.

BACKGROUND: Neurocognitive disorders (NCDs) are a part of the post-acute coronavirus disease (COVID-19) syndrome. No study has specifically evaluated NCDs in post-acute COVID-19 patients with cognitive complaints or their MRI determinants. OBJECTIVE: To characterize NCDs in post-acute COVID-19 patients with cognitive complaints. The secondary objectives were to assess their clinical and MRI determinants. METHODS: We included 46 patients with a post-acute COVID-19 cognitive complaint referred to the Amiens University Hospital Memory Center. They underwent a neuropsychological assessment and 36 had cerebral MRI. The G3 overall summary score was the sum of the mean z scores for the executive function, language, and action speed domains. Neuropsychological profiles were compared in a general linear model. Clinical determinants were analyzed by stepwise linear regression. White matter hyperintensities (WMH) masks were analyzed using parcel-based WMH symptom mapping to identify the locations of WMHs associated with cognitive performance. RESULTS: Repeated ANOVA showed a group effect (p = 0.0001) due to overall lower performance for patients and a domain effect (p = 0.0001) due to a lower (p = 0.007) action speed score. The G3 overall summary score was significantly associated with solely the requirement for oxygen (R2 = 0.319, p = 0.031). WHMs were associated with the G3 overall summary score in the following structures, all right-sided (p < 0.01): superior frontal region, postcentral region, cingulum, cortico-spinal tract, inferior longitudinal fasciculus, internal capsule, and posterior segment of the arcuate fasciculus. CONCLUSION: Post-acute COVID-19 patients with cognitive complaints had NCD, with prominent action slowing, significantly associated with the acute phase oxygen requirement and a right-sided WMH structure pattern.

Effect of Multishell Diffusion MRI Acquisition Strategy and Parcellation Scale on Rich-Club Organization of Human Brain Structural Networks.

The majority of network studies of human brain structural connectivity are based on single-shell diffusion-weighted imaging (DWI) data. Recent advances in imaging hardware and software capabilities have made it possible to acquire multishell (b-values) high-quality data required for better characterization of white-matter crossing-fiber microstructures. The purpose of this study was to investigate the extent to which brain structural organization and network topology are affected by the choice of diffusion magnetic resonance imaging (MRI) acquisition strategy and parcellation scale. We performed graph-theoretical network analysis using DWI data from 35 Human Connectome Project subjects. Our study compared four single-shell (b = 1000, 3000, 5000, 10,000 s/mm2) and multishell sampling schemes and six parcellation scales (68, 200, 400, 600, 800, 1000 nodes) using five graph metrics, including small-worldness, clustering coefficient, characteristic path length, modularity and global efficiency. Rich-club analysis was also performed to explore the rich-club organization of brain structural networks. Our results showed that the parcellation scale and imaging protocol have significant effects on the network attributes, with the parcellation scale having a substantially larger effect. Regardless of the parcellation scale, the brain structural networks exhibited a rich-club organization with similar cortical distributions across the parcellation scales involving at least 400 nodes. Compared to single b-value diffusion acquisitions, the deterministic tractography using multishell diffusion imaging data consisting of shells with b-values higher than 5000 s/mm2 resulted in significantly improved fiber-tracking results at the locations where fiber bundles cross each other. Brain structural networks constructed using the multishell acquisition scheme including high b-values also exhibited significantly shorter characteristic path lengths, higher global efficiency and lower modularity. Our results showed that both parcellation scale and sampling protocol can significantly impact the rich-club organization of brain structural networks. Therefore, caution should be taken concerning the reproducibility of connectivity results with regard to the parcellation scale and sampling scheme.

Multi-scale structural rich-club organization of the brain in full-term newborns: a combined DWI and fMRI study.

Objective.Our understanding of early brain development is limited due to rapid changes in white matter pathways after birth. In this study, we introduced a multi-scale cross-modal approach to investigate the rich club (RC) organization and topology of the structural brain networks in 40 healthy neonates using diffusion-weighted imaging and resting-state fMRI data.Approach.A group independent component analysis was first performed to identify eight resting state networks (RSNs) used as functional modules. A groupwise whole-brain functional parcellation was also performed at five scales comprising 100-900 parcels. The distribution of RC nodes was then investigated within and between the RSNs. We further assessed the distribution of short and long-range RC, feeder and local connections across different parcellation scales.Main results.Sharing the scale-free characteristic of small-worldness, the neonatal structural brain networks exhibited an RC organization at different nodal scales (NSs). The subcortical, sensory-motor and default mode networks were found to be strongly involved in the RC organization of the structural brain networks, especially in the zones where the RSNs overlapped, with an average cross-scale proportion of 45.9%, 28.5% and 10.5%, respectively. A large proportion of the connector hubs were found to be RC members for the coarsest (73%) to finest (92%) NSs. Our results revealed a prominent involvement of cortico-subcortical and cortico-cerebellar white matter pathways in the RC organization of the neonatal brain. Regardless of the NS, the majority (more than 65.2%) of the inter-RSN connections were long distance RC or feeder with an average physical connection of 105.5 and 97.4 mm, respectively. Several key RC regions were identified, including the insula and cingulate gyri, middle and superior temporal gyri, hippocampus and parahippocampus, fusiform gyrus, precuneus, superior frontal and precentral gyri, calcarine fissure and lingual gyrus.Significance.Our results emphasize the importance of the multi-scale connectivity analysis in assessing the cross-scale reproducibility of the connectivity results concerning the global and local topological properties of the brain networks. Our findings may improve our understanding of the early brain development.

Sexual Dimorphisms and Asymmetries of the Thalamo-Cortical Pathways and Subcortical Grey Matter of Term Born Healthy Neonates: An Investigation with Diffusion Tensor MRI.

Diffusion-tensor-MRI was performed on 28 term born neonates. For each hemisphere, we quantified separately the axial and the radial diffusion (AD, RD), the apparent diffusion coefficient (ADC) and the fractional anisotropy (FA) of the thalamo-cortical pathway (THC) and four structures: thalamus (TH), putamen (PT), caudate nucleus (CN) and globus-pallidus (GP). There was no significant difference between boys and girls in either the left or in the right hemispheric THC, TH, GP, CN and PT. In the combined group (boys + girls) significant left greater than right symmetry was observed in the THC (AD, RD and ADC), and TH (AD, ADC). Within the same group, we reported left greater than right asymmetry in the PT (FA), CN (RD and ADC). Different findings were recorded when we split the group of neonates by gender. Girls exhibited right > left AD, RD and ADC in the THC and left > right FA in the PT. In the group of boys, we observed right > left RD and ADC. We also reported left > right FA in the PT and left > right RD in the CN. These results provide insights into normal asymmetric development of sensory-motor networks within boys and girls.

Fold-Over Oversampling Effects in the Measurements of Cerebral Cerebrospinal Fluid and Blood Flows with 2D Cine Phase-Contrast MRI.

This prospective study investigated the effects of fold-over oversampling on phase-offset background errors with 2D-Cine phase contrast (Cine-PC) magnetic resonance imaging (MRI). It was performed on brain MRI and compared to conventional Full-field of view FOV coverage and it was tested with two different velocity encoding (Venc) values. We chose Venc = 100 mm/s to encode cerebrospinal fluid (CSF) flows in the aqueduct and 600 mm/s to encode blood flow in the carotid artery. Cine-PC was carried out on 10 healthy adult volunteers followed simultaneously by an acquisition on static agar-gel phantom to measure the phase-offset background errors. Pixel-wise correction of both the CSF and the blood flows was calculated through 32 points of the cardiac-cycle. We compared the velocity-to-noise ratio, the section area, the absolute and the corrected velocity (peak; mean and minimum), the net flow, and the stroke volume before and after correction. We performed the statistical T-test to compare Full-FOV and fold-over and Bland-Altman plots to analyze their differences. Our results showed that following phase-offset error correction, the blood stroke-volume was significantly higher with Full-FOV compared to fold-over. We observed a significantly higher CSF mean velocity and net flow values in the fold-over option. Compared to Full-FOV, fold-over provides a significantly larger section area and significantly lower peak velocity-offset in the aqueduct. No significant difference between the two coverages was reported before and after phase-offset in blood flow measurements. In conclusion, fold-over oversampling can be chosen as an alternative to increase spatial resolution and accurate cerebral flow quantification in Cine-PC.

Network based statistics reveals trophic and neuroprotective effect of early high dose erythropoetin on brain connectivity in very preterm infants.

Periventricular white matter injury is common in very preterm infants and it is associated with long term neurodevelopmental impairments. While evidence supports the protective effects of erythropoetin (EPO) in preventing injury, we currently lack the complete understanding of how EPO affects the emergence and maturation of anatomical brain connectivity and function. In this case-control study, connectomic analysis based on diffusion MRI tractography was applied to evaluate the effect of early high-dose EPO in preterm infants. A whole brain, network-level analysis revealed a sub-network of anatomical brain connections in which connectivity strengths were significantly stronger in the EPO group. This distributed network comprised connections predominantly in the frontal and temporal lobe bilaterally, and the effect of EPO was focused on peripheral and feeder connections of the core structural connectivity network. EPO resulted in a globally increased clustering coefficient, higher global and average local efficiency, while higher strength and increased clustering was found for regions in the frontal lobe and cingulate gyrus. The connectivity network most affected by the EPO treatment showed a steeper increase graph theoretical measures with age compared to the placebo group. Our results demonstrate a weak but widespread effect of EPO on the structural connectivity network and a possible trophic effect of EPO reflected by increasing network segregation, predominantly in local connections.

Total cerebrovascular blood flow and whole brain perfusion in children sedated using propofol with or without ketamine at induction: An investigation with 2D-Cine PC and ASL.

BACKGROUND: Multiple sedation regimes may be used to facilitate pediatric MRI scans. These regimes might affect cerebral blood flow and hemodynamics to varying degrees, particularly in children who may be vulnerable to anesthetic side effects. PURPOSE: To compare the effects of propofol monosedation solely (Pm group) vs. a combination of propofol and ketamine (KP group) on brain hemodynamics and perfusion. STUDY TYPE: Prospective double-blind randomized trial. FIELD STRENGTH/SEQUENCES: 1.5T and 3T. 2D-Cine phase contrast (2D-Cine PC) and pseudocontinuous arterial spin labeling (ASL). POPULATION: Children aged from 3 months to 10 years referred for MRI with deep sedation were randomized into either the KP or the Pm group. Perfusion images were acquired with ASL followed by single-slice 2D-Cine PC acquired between the cervical vertebra C2 and C3. ASSESSMENT: Average whole-brain perfusion (WBP ml.min-1 .100 ml-1 ) was extracted from the ASL perfusion maps and total cerebrovascular blood flow (CVF) was quantified by bilaterally summing the flow in the vertebral and the internal carotid arteries. The CVF values were converted to units of ml.min-1 .100 g-1 to calculate the tissue CVF100g (ml.min-1 .100 g-1 ). Images were assessed by a neuroradiologist and data from n = 81 (ASL) and n = 55 (PC) cases with no apparent pathology were entered into the analysis. STATISTICAL TESTS: Multivariate analysis of covariance was performed to compare drug sedation effects on WBP, CVF, and CVF100g . RESULTS: No significant difference in arterial flow was observed (P = 0.57), but the KP group showed significantly higher WBP than the Pm group, covarying for scanner and age (P = 0.003). A correlation analysis showed a significant positive correlation between mean WBP (ml.min-1 .100 g-1 ) and mean CVF100g . DATA CONCLUSION: The KP group showed higher perfusion but no significant difference in vascular flow compared with the Pm group. WBP and CVF100g correlated significantly, but ASL appeared to have more susceptibility to perfusion differences arising from the different sedation regimes. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2019;50:1433-1440.

Early assessment of lateralization and sex influences on the microstructure of the white matter corticospinal tract in healthy term neonates.

We assessed the sex and the lateralization differences in the corticospinal tract (CST) during the early postnatal period. Twenty-five healthy term neonates (13 girls, aged 39.2 ± 1.2 weeks, and 12 boys aged 38.6 ± 3.0 weeks) underwent Diffusion Tensor Imaging (DTI). Fiber tracking was performed to extract bilaterally the CST pathways and to quantify the parallel (E1 ) and perpendicular (E23 ) diffusions, the apparent diffusion coefficient (ADC), and fractional anisotropy (FA). The measurements were performed on the entire CST fibers and on four segments: base of the pons (CST-Po), cerebral peduncles (CST-CP), posterior limb of the internal capsule (CST-PLIC), and corona-radiata (CST-CR). Significantly higher E1 , lower E23, and higher FA in the right compared to the left were noted in the CST-PLIC of the girls. Significantly lower E23 and lower ADC with higher FA in the right compared to left were observed in the CST-CP of the boys. Moreover, the CST-PLIC of the boys had significantly higher E1 in the right compared to the left. There was a significant increase in left CST E1 of boys when compared with girls. Girls had a significantly lower E1 , lower E23 and, lower ADC in the left CST-CP compared with boys. In addition, girls had a significantly lower E23 and higher FA in the right CST-PLIC compared with boys. Sex differences and lateralization in structure-based segments of the CST were found in healthy term infants during early postnatal period. These findings are vital to understanding motor development of healthy term born neonates to better interpret newborn infants with abnormal neurodevelopment.

Sedation for magnetic resonance imaging using propofol with or without ketamine at induction in pediatrics-A prospective randomized double-blinded study.

INTRODUCTION: Deep sedation using propofol has become a standard technique in children. This double-blinded randomized clinical trial aims to compare the clinical effects of propofol-mono-sedation vs a combination of propofol and ketamine at induction and a reduced propofol infusion rate for maintenance in children undergoing diagnostic magnetic resonance imaging. METHODS: Children aged from 3 months to 10 years scheduled as outpatients for elective magnetic resonance imaging with deep sedation were included. They were randomized into 2 groups, receiving either 1 mg/kg ketamine at induction, then a propofol infusion rate of 5 mg/kg/h or a propofol infusion rate of 10 mg/kg/h without prior ketamine. Time to full recovery (modified Aldrete score = 10) was the primary outcome. Further outcomes were quality of induction, immobilization during image acquisition, recovery, postoperative nausea and vomiting, emergence delirium using the Pediatric Anesthesia Emergence Delirium scale, vital signs and adverse cardiorespiratory events. All patients and parents as well as anesthetists, imaging technicians, and postsedation personnel were blinded. Data are given as median (range). RESULTS: In total, 347 children aged 4.0 (0.25-10.9) years, weighing 15.6 (5.3-54) kg, ASA classification I, II, or III (141/188/18) were included. The ketamine-propofol group showed significantly shorter recovery times (38 (22-65) vs 54 (37-77) minutes; median difference 14 (95% CI: 8, 20) minutes; P < .001), better quality of induction, and higher blood pressure, but higher incidence of movement requiring additional sedative drugs. There were no significant differences in respiratory side effects, cardiovascular compromise, emergence delirium, or postoperative nausea and vomiting. CONCLUSION: Both sedation concepts proved to be reliable with a low incidence of side effects. Ketamine at induction with a reduced propofol infusion rate leads to faster postanesthetic recovery.

Regional differences in interhemispheric structural fibers in healthy, term infants.

Using fiber tracking we investigated the early interhemispheric to cortical development by segmenting the corpus callosum (CC) in five substructures, genu, rostrum, body, isthmus, and splenium, and to examine gender differences in healthy, term neonates. Twenty neonates (11 boys aged 39 ± 2 days, nine girls aged 39 ± 1 days) were scanned in natural sleep with diffusion tensor imging and 35 gradient directions. Fiber tracking was performed using the FACT algorithm. The CC was segments in five substructures on midsagittal imaging. The fiber axial and radial diffusion were measured along with apparent diffusion coefficient and fractional anisotropy. Volume measures were performed for each of these substructures using high-resolution isotropic 3D T1-weighted images. Radial and mean diffusivity in all measured interhemispheric connections were significantly higher in male newborn infants than in female. Second, a gender-dependent regional difference of the measured interhemispheric connections exists. There was no volume difference between boys and girls in any of the five studied sudsubstructures. In addition there was no association between macrostructural and microstructural differences either in boys or girls. The cytoarchitecture and the integrity of the interhemispheric fibers is more developed in female infants in all subdivisions of the CC, except for the isthmus. This might result from a larger axonal diameter, highly packed fibers, or more well-developed myelin sheath. © 2016 Wiley Periodicals, Inc.

Regional Microstructural and Volumetric Magnetic Resonance Imaging (MRI) Abnormalities in the Corpus Callosum of Neonates With Congenital Heart Defect Undergoing Cardiac Surgery.

The purpose of the study is to investigate the structural development of the corpus callosum in term neonates with congenital heart defect before and after surgery using diffusion tensor imaging and 3-dimensional T1-weighted magnetic resonance imaging (MRI). We compared parallel and radial diffusions, apparent diffusion coefficient (ADC), fractional anisotropy, and volume of 5 substructures of the corpus callosum: genu, rostral body, body, isthmus, and splenium. Compared to healthy controls, we found a significantly lower volume of the splenium and total corpus callosum and a higher radial diffusion and lower fractional anisotropy in the splenium of patients presurgery; a lower volume in all substructures in the postsurgery group; higher radial diffusion in the rostral body, body, and splenium; and a higher apparent diffusion coefficient in the splenium of postsurgery patients. Similar fractional anisotropy changes in congenital heart defect patients were reported in preterm infants. Our findings in apparent diffusion coefficient in the splenium of these patients (pre and postsurgery) are comparable to findings in preterm neonates with psychomotor delay. Delayed maturation of the isthmus was also reported in preterm infants.

Diffusion tensor imaging of patients with proteolipid protein 1 gene mutations.

Pelizaeus-Merzbacher disease (PMD) is an X-linked disorder of the central nervous system (CNS) caused by a wide variety of mutations affecting proteolipid protein 1 (PLP1). We assessed the effects of PLP1 mutations on water diffusion in CNS white matter by using diffusion tensor imaging. Twelve patients with different PLP1 point mutations encompassing a range of clinical phenotypes were analyzed, and the results were compared with a group of 12 age-matched controls. The parallel (λ// ), perpendicular (λ⊥ ), and apparent diffusion coefficients (ADC) and fractional anisotropy were measured in both limbs of the internal capsule, the genu and splenium of corpus callosum, the base of the pons, and the cerebral peduncles. The mean ADC and λ⊥ in the PMD patient group were both significantly increased in all selected structures, except for the base of the pons, compared with controls. PMD patients with the most severe disease, however, had a significant increase of both λ// and λ⊥ . In contrast, more mildly affected patients had much smaller changes in λ// and λ⊥ . These data suggest that myelin, the structure responsible in part for the λ⊥ barrier, is the major site of disease pathogenesis in this heterogeneous group of patients. Axons, in contrast, the structures mainly responsible for λ// , are much less affected, except within the subgroup of patients with the most severe disease. Clinical disability in patients with PLP1 point mutation is thus likely determined by the extent of pathological involvement of both myelin and axons, with alterations of both structures causing the most severe disease. © 2014 Wiley Periodicals, Inc.

Insights into cerebrospinal fluid and cerebral blood flows in infants and young children.

This study investigates the craniospinal flows of blood and cerebrospinal fluid using phase-contrast magnetic resonance imaging (MRI) on 23 control neonates and infants (5 d-68 mo old). Mean arterial cerebral blood flow increased with age of infant from 180 mL/min after birth to 1330 mL/min around 6 years of age. This corresponds to 51 mL/min/100 g and 95 mL/min/100 g, respectively. Cervical cerebrospinal fluid stroke volume increased from 38 × 10(-3) mL to 752 × 10(-3) mL per cardiac cycle. After arterial systolic blood inflow, we observed a delay of the venous outflow that was always preceded by cerebrospinal fluid flushing out through the spinal canal. These results highlighted the importance of compliance of the spinal compartment and the interaction of blood and cerebrospinal fluid dynamics. The capacity of the spinal compartment to receive intracranial cerebrospinal fluid in presence of fontanels was demonstrated. We provide reference values to understand the physiology of cerebrospinal fluid and cerebral blood.

An innovative approach to investigate the dynamics of the cerebrospinal fluid in the prepontine cistern: A feasibility study using spatial saturation-prepared cine PC-MRI.

PURPOSES: Accurate measurements of the cerebrospinal fluid that flows through the prepontine cistern (PPC) are challenging due to artefacts originating from basilar artery blood flow. We aim to accurately quantify cerebrospinal fluid (CSF) flow and stroke volume in the PPC, which is essential before endoscopic third ventriculostomy. MATERIALS AND METHODS: We developed a new PC-MRI sequence prepared with Hadamard saturation bands to accurately quantify CSF flow in the PPC by suppressing the blood signal in the surrounding vessels. In total, 28 adult hydrocephalic patients (age 59 ± 20 years) were scanned using conventional PC-MRI and our developed sequence. CSF was separately extracted from the PPC and the foramen of Magendie, and flow (min and max) and stroke volume were quantified. RESULTS: Our modifications result in a complete deletion of signal from flowing blood, resulting in significantly reduced CSF stroke volume (Conv = 446 ± 113 mm(3), Dev = 390 ± 119 mm(3), p = 0.006) and flow, both minimum (Conv = -1630 ± 486 mm(3)/s, Dev = -1430 ± 406 mm(3)/s, p = 0.005) and maximum (Conv = 2384 ± 657 mm(3)/s, Dev = 1971 ± 62 mm(3)/s, p = 0.002) compared with the conventional sequence, whereas no change in the area of interest was noted (Conv = 236 ± 65 mm(2), Dev = 249 ± 75 mm(2), p = 0.21). CONCLUSIONS: Accurate and reproducible CSF flow and stroke volume measurements in the PPC can be achieved with sat-band prepared cine PC-MRI.

The role of the thalamus in neuro-cognitive dysfunction in early unilateral hemispheric injury: a multimodality imaging study of children with Sturge-Weber syndrome.

BACKGROUND: Sturge-Weber syndrome (SWS) with unilateral hemispheric involvement is a clinical model of early onset, chronic, often progressive hemispheric injury, resulting in variable neuro-cognitive impairment. AIMS: To evaluate if abnormal diffusion and metabolism of the thalamus, a central relay station with extensive cortical connections, may serve as a simple imaging marker of neuro-cognitive dysfunction in SWS. METHODS: We obtained both diffusion tensor imaging and FDG PET in 20 children (11 girls; age range: 3-12.4 years) with unilateral SWS. Diffusion parameters as well as FDG uptake were measured in thalami, compared to normal control values, and correlated with the extent of cortical hypometabolism, deep venous abnormalities and cognitive (IQ) as well as fine motor functions. RESULTS: Children with SWS had significantly higher thalamic glucose metabolic asymmetry than controls (p=0.001). Thalamic metabolic asymmetries correlated positively with the asymmetry of thalamic diffusivity (p=0.001) and also with the extent of cortical hypometabolism (p<0.001). Severe thalamic asymmetries of glucose metabolism and diffusion were strong predictors of low IQ (metabolism: p=0.002; diffusivity: p=0.01), even after controlling for age and extent of cortical glucose hypometabolism in children with left hemispheric involvement. Ipsilateral thalamic glucose hypometabolism was also associated with impairment of fine motor functions (p=0.002). CONCLUSIONS: Both diffusion and glucose metabolic abnormalities of the thalamus are closely related to cognitive functions, independent of age and cortical metabolic abnormalities, in children with unilateral SWS. Thalamic metabolic asymmetry is a robust but simple imaging marker of neuro-cognitive outcome in children with early unilateral hemispheric injury caused by Sturge-Weber syndrome.

Abnormal water diffusivity in corticostriatal projections in children with Tourette syndrome.

The fronto-striato-thalamic circuit has been implicated in the pathomechanism of Tourette Syndrome (TS). To study white and gray matter comprehensively, we used a novel technique called Tract-Based Spatial Statistics (TBSS) combined with voxel-based analysis (VBA) of diffusion tensor MR images in children with TS as compared to typically developing controls. These automated and unbiased methods allow analysis of cerebral white matter and gray matter regions. We compared 15 right-handed children with TS (mean age: 11.6 ± 2.5 years, 12 males) to 14 age-matched right-handed healthy controls (NC; mean age: 12.29 ± 3.2 years, 6 males). Tic severity and neurobehavioral scores were correlated with FA and ADC values in regions found abnormal by these methods. For white matter, TBSS analysis showed regions of increased ADC in the corticostriatal projection pathways including left external capsule and left and right subcallosal fasciculus pathway in TS group compared to NC group. Within the TS group, ADC for the left external capsule was negatively associated with tic severity (r= -0.586, P = 0.02). For gray matter, VBA revealed increased ADC for bilateral orbitofrontal cortex, left putamen, and left insular cortex. ADC for the right and left orbitofrontal cortex was highly correlated with internalizing problems (r = 0.665; P = 0.009, r = 0.545; P = 0.04, respectively). Altogether, this analysis revealed focal diffusion abnormalities in the corticostriatal pathway and in gray matter structures involved in the fronto-striatal circuit in TS. These diffusion abnormalities could serve as a neuroimaging marker related to tic severity and neurobehavioral abnormalities in TS subjects.

Multimodality neuroimaging in Tourette syndrome: alpha-[11C] methyl-L-tryptophan positron emission tomography and diffusion tensor imaging studies.

Previous studies in Tourette syndrome have reported lateralized abnormalities of neurotransmitters and microstructure of the cortico-striato-thalamo-cortical circuit. The authors analyzed the relationship between serotonin synthesis and microstructural changes in the subcortical structures (caudate nucleus, lentiform nucleus, and thalamus) related to this circuit, using alpha-[(11)C]methyl-L-tryptophan positron emission tomography (PET) and diffusion tensor imaging, respectively, in 16 children with Tourette syndrome. Correlations between diffusion tensor imaging and alpha-[(11)C]methyl-L-tryptophan PET asymmetry values were found in the caudate nucleus. The findings suggested higher serotonin synthesis on the side of more abnormal diffusion, characterized by lower fractional anisotropy and parallel diffusivity but higher perpendicular diffusivity. Altogether, these imaging abnormalities suggest asymmetric immature microstructure in the caudate nucleus associated with abnormally increased serotonin synthesis in Tourette syndrome. The observed diffusion tensor imaging changes are likely related to abnormal connectivity in the cortico-striato-thalamo-cortical circuit, which may result in cortical disinhibition and increased serotonin synthesis; this could provide a new therapeutic target.