Diffusion Tensor Imaging Magnetic Resonance Imaging Research Articles

Abnormal functional-structural cingulum connectivity in mania: combined functional magnetic resonance imaging-diffusion tensor imaging investigation in different phases of bipolar disorder.

The objective of the study was to investigate the relationship between structural connectivity (SC) and functional connectivity (FC) in the cingulum in bipolar disorder (BD) and its various phases. We combined resting-state functional magnetic resonance imaging and probabilistic tractographic diffusion tensor imaging to investigate FC and SC of the cingulum and its portions, the SC-FC relationship, and their correlations with clinical and neurocognitive measures on sustained attention in manic (n = 21), depressed (n = 20), and euthymic (n = 20) bipolar patients and healthy controls (HC) (n = 42). First, we found decreased FC between the anterior and posterior parts of the cingulum in manic patients when compared to depressed patients and HC. Second, we observed decreased SC of the cingulum bundle, particularly in its anterior part, in manic patients when compared to HC. Finally, alterations in the cingulum FC (but not SC) correlated with clinical severity scores while changes in the cingulum SC (but not FC) were related with neurocognitive deficits in sustained attention in BD. We demonstrate for the first time a reduction in FC and concomitantly in SC of the cingulum in mania, which correlated with psychopathological and neurocognitive parameters, respectively, in BD. This supports the central role of cingulum connectivity specifically in mania.

Abstract 16541: Abnormal Brain Connectivity and Poor Neurodevelopmental Outcome in Congenital Heart Disease Patients With Subtle Brain Dysplasia

Introduction: Mutant mouse models with congenital heart disease (CHD) were observed to have distinct brain dysplasia, prompting an assessment for brain anomalies in CHD patients. CHD infants with brain magnetic resonance imaging (MRI) assessments were recruited and scored using a novel brain dysplasia index. Validation was conducted with parallel brain connectome analysis and neurodevelopment outcome assessments. Methods: The Ohia mutant mouse line and others were analyzed for brain defects using 3D episcopic confocal histopathology. In parallel, we recruited 220 CHD neonates with MRI scans from two large centers. This included pre and postoperative conventional MRI sequences and diffusion tensor imaging (DTI). Brain connectivity measurements with DTI-graph analysis and neurodevelopmental testing at 18 months of age (Battelle Developmental Inventory) were obtained. Results: The CHD mouse mutant analysis revealed high prevalence of brain dysplasia involving the olfactory bulb, cerebellum, hippocampus, corpus callosum and choroid plexus. Based on these findings, a brain dysplasia index (BDI) was developed for clinical assessment of CHD patients, with one point for abnormality in any of these structures right or left and for presence of extra-axial cerebral spinal fluid. Analysis of 220 CHD neonates yielded BDI scores ranging from 1 to 17, with average score of 4.1. An elevated BDI score was seen across a spectrum of cardiac lesions, and was similar pre-op and post-op. DTI graph connectivity measurements (reduced nodal efficiency) correlated with high BDI score (p<0.05), but not to specific heart lesions or white matter injury. Neurodevelopmental assessment of 20 patients at 18 months showed higher BDI score correlated with reduction in Total Developmental Quotient (p <0.05) and Adaptive Developmental Quotient (p<0.009). Conclusion: A brain dysplasia index was developed based on brain anomalies seen in CHD mutant mouse models. Infants with CHD of a broad spectrum with high BDI score showed abnormal brain connectivity and poor neurodevelopmental outcome. These findings suggest the poor neurodevelopmental outcome associated with CHD may involve subtle brain dysplasia with a shared developmental etiology with the structural heart disease.

Editorial on emerging neuroimaging tools for studying normal and abnormal human brain development.

Research on human brain development has seen an upturn in the past few years due to increasing use of noninvasive neuroimaging tools for studying the anatomy and function of the developing brain. Here we gathered innovative studies of human brain function and development using magnetic resonance imaging (MRI), near infrared spectroscopy (NIRS) and magnetoencephalography (MEG) with experimental paradigms suitable for pediatric research. These modalities are without significant risk to the developing brain, generally require minimal patient preparation, and are well tolerated by children when performed by experienced teams. A review of recent studies of human brain development using these advanced neuroimaging tools is quite timely, since we are witnessing advances not only in the instrumentation optimized for the pediatric population, but also in research focused on the human fetuses in utero, neonates, and older children. MRI methods such volumetric T1 imaging and Diffusion Tensor Imaging (DTI) are being used more frequently in children to determine the gross anatomy and structural connectivity of the developing brain. Functional MRI and NIRS are being used to assess the hemodynamics of neurovascular responses and functional localization in development (Govindan et al., 2014; Horowitz-Kraus et al., 2014). MEG complements electroencephalography (EEG) as the only other technique capable of directly measuring the developing brain neural activity in an entirely passive manner with MEG being superior to EEG in its ability to localize activity during development. MEG and EEG can be used to assess electrophysiological functions of the developing human brain (Edgar et al., 2014). Findings from multiple neuroimaging methods can be combined to answer specific scientific questions regarding pediatric pathology (Brown et al., 2014; Hunold et al., 2014; Papadelis et al., 2014) or typical human brain development. Although MEG is still being used relatively rarely in pediatric studies, recent developments in this technology (Roberts et al., 2014) are beginning to demonstrate its utility in both the basic and clinical neuroscience of brain development (Edgar et al., 2014; Rezaie et al., 2014; Sowman et al., 2014; Taylor et al., 2014). Biomagnetic techniques also offer a direct noninvasive way to assess the functional brain and heart activity of human fetuses in utero. Unlike electric fields, magnetic fields produced by the electrical activity in the heart and brain of the fetus are not attenuated by the vernix, a waxy film covering its entire skin. Biomagnetic instruments specifically designed for fetal studies have been developed for this purpose. Fetal MEG studies using such a system have shown that both spontaneous brain activity and evoked cortical activity can be measured from outside the abdomen of pregnant mothers (Muenssinger et al., 2013). Fetal MEG and Magnetocardiography (MCG) may become clinically very useful for implementation and evaluation of intervention programs in at-risk populations. Biomagnetic instruments have also been developed for specifically measuring the brain activity in newborns, infants, and older children (Roberts et al., 2014). MEG studies have shown the usefulness of MEG for localizing active regions in the brain and also for tracking the longitudinal maturation of various sensory systems. Studies of pediatric patients are beginning to show interesting functional pathology in autism spectrum disorder (Doesburg et al., 2013; Edgar et al., 2014), cerebral palsy (Papadelis et al., 2014), epilepsy (Hunold et al., 2014; Khan et al., 2014; Tanaka and Stufflebeam, 2014), and other neurological and psychiatric disorders (Down syndrome, traumatic brain injury, Tourette syndrome, hearing deficits, childhood migraine) (Larson and Lee, 2014). The current research topic gathers studies from different research groups studying the human brain development by using advanced neuroimaging tools. Neuroimaging can offer critical information about both normal as well as abnormal human brain development. Most of the currently available tools are designed for adult use. Hardware and methods especially tailored for pediatric use remain under continual refinement. Issues relating to compliance are now mitigated by new software developments such as head motion tracking and motion correction. Such technological advancements to address specific issues germane to pediatric populations will likely promote wider adoption of neuroimaging for both clinical as well as research purposes.

Correction of hyponatraemia improves cognition, quality of life, and brain oedema in cirrhosis

Hyponatraemia in cirrhosis is associated with impaired cognition and poor health-related quality of life (HRQOL). However, the benefit of hyponatraemia correction is unclear. The aim of this study was to evaluate the effect of tolvaptan on serum sodium (Na), cognition, HRQOL, companion burden, and brain MRI (volumetrics, spectroscopy, and diffusion tensor imaging) in cirrhotics with hyponatraemia. Cirrhotics with Na <130 mEq/L were included for a four-week trial. At screening, patients underwent cognitive and HRQOL testing, serum/urine chemistries and companion burden assessment. Patients then underwent fluid restriction and diuretic withdrawal for two weeks after which cognitive tests were repeated. If Na was still <130 mEq/L, brain magnetic resonance imaging (MRI) was performed and tolvaptan was initiated for 14 days with frequent clinical/laboratory monitoring. After 14 days of tolvaptan, all tests were repeated. Comparisons were made between screen, pre-and post-drug periods Na, urine/serum laboratories, cognition, HRQOL and companion burden. 24 cirrhotics were enrolled; seven normalized Na without tolvaptan with improvement in cognition. The remaining 17 received tolvaptan of which 14 completed the study over 13 ± 2 days (age 58 ± 6 years, MELD 17, 55% HCV, median 26 mg/day of tolvaptan). Serum Na and urine free water clearance increased with tolvaptan without changes in mental status or liver function. Cognitive function, HRQOL and companion burden only improved in these 14 patients after tolvaptan, along with reduced total brain and white matter volume, increase in choline on magnetic resonance spectroscopy, and reduced cytotoxic oedema. Short-term tolvaptan therapy is well tolerated in cirrhosis. Hyponatraemia correction is associated with cognitive, HRQOL, brain MRI and companion burden improvement.

White matter changes in preclinical Alzheimer's disease: a magnetic resonance imaging-diffusion tensor imaging study on cognitively normal older people with positive amyloid β protein 42 levels

The aim of this study was to use diffusion tensor imaging measures to determine the existence of white matter microstructural differences in the preclinical phases of Alzheimer's disease, assessing cognitively normal older individuals with positive amyloid β protein (Aβ42) levels (CN_Aβ42+) on the basis of normal cognition and cerebrospinal fluid Aβ42 levels below 500 pg/mL. Nineteen CN_Aβ42+ and 19 subjects with Aβ42 levels above 500 pg/mL (CN_Aβ42−) were included. We encountered increases in axial diffusivity (AxD) in CN_Aβ42+ relative to CN_Aβ42− in the corpus callosum, corona radiata, internal capsule, and superior longitudinal fasciculus bilaterally, and also in the left fornix, left uncinate fasciculus, and left inferior fronto-occipital fasciculus. However, no differences were found in other diffusion tensor imaging indexes. Cognitive reserve scores were positively associated with AxD exclusively in the CN_Aβ42+ group. The finding of AxD alteration together with preserved fractional anisotropy, mean diffusivity, and radial diffusivity indexes in the CN_Aβ42+ group may indicate that, subtle axonal changes may be happening in the preclinical phases of Alzheimer's disease, whereas white matter integrity is still widely preserved.

Diffusion Tensor Imaging and Resting-State Functional MRI-Scanning in 5- and 6-Year-Old Children: Training Protocol and Motion Assessment

Advanced Magnetic Resonance Imaging (MRI) techniques such as Diffusion Tensor Imaging (DTI) and resting-state functional MRI (rfMRI) are widely used to study structural and functional neural connectivity. However, as these techniques are highly sensitive to motion artifacts and require a considerable amount of time for image acquisition, successful acquisition of these images can be challenging to complete with certain populations. This is especially true for young children. This paper describes a new approach termed the ‘submarine protocol’, designed to prepare 5- and 6-year-old children for advanced MRI scanning. The submarine protocol aims to ensure that successful scans can be acquired in a time- and resource-efficient manner, without the need for sedation. This manuscript outlines the protocol and details its outcomes, as measured through the number of children who completed the scanning procedure and analysis of the degree of motion present in the acquired images. Seventy-six children aged between 5.8 and 6.9 years were trained using the submarine protocol and subsequently underwent DTI and rfMRI scanning. After completing the submarine protocol, 75 of the 76 children (99%) completed their DTI-scan and 72 children (95%) completed the full 35-minute scan session. Results of diffusion data, acquired in 75 children, showed that the motion in 60 of the scans (80%) did not exceed the threshold for excessive motion. In the rfMRI scans, this was the case for 62 of the 71 scans (87%). When placed in the context of previous studies, the motion data of the 5- and 6-year-old children reported here were as good as, or better than those previously reported for groups of older children (i.e., 8-year-olds). Overall, this study shows that the submarine protocol can be used successfully to acquire DTI and rfMRI scans in 5 and 6-year-old children, without the need for sedation or lengthy training procedures.

Quantitative evaluation of the axonal degeneration of central motor neurons in chronic cerebral stroke with diffusion tensor imaging

Conventional magnetic resonance imaging (MRI) can only show the degeneration-induced morphological changes but fail to quantitatively reveal the degree and extent of the axonal damage of nerve fibers. Diffusion tensor imaging (DTI) has the ability to detect the diffusion of water molecules and thus suitable to the study of axonal degeneration of central motor neurons. To illustrate and quantitatively evaluate the axonal degeneration of central motor neurons in patients with chronic cerebral stroke. DTI and conventional MRI were carried out with 10 normal control subjects and 25 patients who suffered from chronic cerebral stroke in the region supplied by middle cerebral artery and had varying degrees of limb movement disorders (the mean time of onset was 2.5 months), to measure the fractional anisotropy (FA), volume ratio (VR), apparent diffusion coefficient (ADC), tensor eigenvalues (λ1, λ2, and λ3), and signal intensity (SI) on T2-weighted images, of the central motor fibers (pyramidal tract) in the plane of cerebral peduncle. Results from the ipsilateral side were compared with those from the contralateral side in the same patient and with those from normal control. The axonal degeneration of central motor neurons manifests in DTI as the decline of FA of the pyramidal tract and the reduction and distortion of the high signal area. While all the FA, VR, ADC, and λ1 in the ipsilateral side reduce on DTI, λ3 increases; the T2-weighted signals exhibit no significant differences among groups. The changes and diffusions of water molecule associated with the axonal degeneration of central motor neurons after chronic cerebral stroke can be detected by DTI, which can directly quantitatively reflect the degree and extent of axonal degeneration of central motor neurons and can compensate the shortcomings of conventional MRI and diffusion-weighted imaging (DWI).

Snipping at the Endophenotypic Space

Snipping at the Endophenotypic Space

Diffusion tensor and volumetric magnetic resonance imaging using an MR-compatible hand-induced robotic device suggests training-induced neuroplasticity in patients with chronic stroke

Stroke is the third leading cause of mortality and a frequent cause of long-term adult impairment. Improved strategies to enhance motor function in individuals with chronic disability from stroke are thus required. Post-stroke therapy may improve rehabilitation and reduce long-term disability; however, objective methods for evaluating the specific impact of rehabilitation are rare. Brain imaging studies on patients with chronic stroke have shown evidence for reorganization of areas showing functional plasticity after a stroke. In this study, we hypothesized that brain mapping using a novel magnetic resonance (MR)-compatible hand device in conjunction with state-of-the-art magnetic resonance imaging (MRI) can serve as a novel biomarker for brain plasticity induced by rehabilitative motor training in patients with chronic stroke. This hypothesis is based on the premises that robotic devices, by stimulating brain plasticity, can assist in restoring movement compromised by stroke-induced pathological changes in the brain and that these changes can then be monitored by advanced MRI. We serially examined 15 healthy controls and 4 patients with chronic stroke. We employed a combination of diffusion tensor imaging (DTI) and volumetric MRI using a 3-tesla (3T) MRI system using a 12-channel Siemens Tim coil and a novel MR-compatible hand-induced robotic device. DTI data revealed that the number of fibers and the average tract length significantly increased after 8 weeks of hand training by 110% and 64%, respectively (p<0.001). New corticospinal tract (CST) fibers projecting progressively closer to the motor cortex appeared during training. Volumetric data analysis showed a statistically significant increase in the cortical thickness of the ventral postcentral gyrus areas of patients after training relative to pre-training cortical thickness (p<0.001). We suggest that rehabilitation is possible for a longer period of time after stroke than previously thought, showing that structural plasticity is possible even after 6 months due to retained neuroplasticity. Our study is an example of personalized medicine using advanced neuroimaging methods in conjunction with robotics in the molecular medicine era.

Structural brain changes after 4 wk of unilateral strength training of the lower limb

Strength training enhances muscular strength and neural drive, but the underlying neuronal mechanisms remain unclear. This study used magnetic resonance imaging (MRI) to identify possible changes in corticospinal tract (CST) microstructure, cortical activation, and subcortical structure volumes following unilateral strength training of the plantar flexors. Mechanisms underlying cross-education of strength in the untrained leg were also investigated. Young, healthy adult volunteers were assigned to training (n = 12) or control (n = 9) groups. The 4 wk of training consisted of 16 sessions of 36 unilateral isometric plantar flexions. Maximum voluntary isometric contraction torque was tested pre- and posttraining. MRI investigation included a T1-weighted scan, diffusion tensor imaging and functional MRI. Probabilistic fiber tracking of the CST was performed on the diffusion tensor imaging images using a two-regions-of-interest approach. Fractional anisotropy and mean diffusivity were calculated for the left and right CST in each individual before and after training. Standard functional MRI analyses and volumetric analyses of subcortical structures were also performed. Maximum voluntary isometric contraction significantly increased in both the trained and untrained legs of the training group, but not the control group. A significant decrease in mean diffusivity was found in the left CST following strength training of the right leg. No significant changes were detected in the right CST. No significant changes in cortical activation were observed following training. A significant reduction in left putamen volume was found after training. This study provides the first evidence for strength training-related changes in white matter and putamen in the healthy adult brain.

Adolescents with d-transposition of the great arteries repaired in early infancy demonstrate reduced white matter microstructure associated with clinical risk factors

Our objective was to use diffusion tensor imaging (DTI) to compare white matter microstructure in adolescents with D-transposition of the great arteries (D-TGA) who underwent the arterial switch operation in early infancy with typically developing control adolescents. We also examined correlates between patient demographic and medical risk factors and white matter as assessed by regional fractional anisotropy (FA) values. We used with magnetic resonance imaging (MRI) to study 49 adolescents with D-TGA and 29 control adolescents. MRI data, including whole brain DTI and conventional anatomic MRI, were acquired from each subject. Each subject's data were analyzed using random effects analysis to evaluate regional white matter differences in FA between D-TGA and control adolescents. While multifocal punctate MRI hypointensities on T1-weighted (T1W) imaging suggestive of mineralization were found, other evidence of gross white matter injury was absent. Eighteen discrete regions of significantly reduced FA in D-TGA adolescents compared with controls were observed in deep white matter of cerebral hemispheres, cerebellum, and midbrain. Among D-TGA adolescents, lower FA correlated with younger gestational age, shorter duration of intraoperative cooling, higher intraoperative minimum tympanic temperature, longer intensive care unit stay after repair, and greater total number of open cardiac operations. Despite scant white matter injury evident on conventional brain MRI, adolescents with D-TGA repaired in infancy demonstrate significant white matter FA reduction that may relate to their reported neurocognitive deficits. Among adolescents with D-TGA, FA values are associated with patient and perioperative factors, some of which are modifiable.

A primer of neuroimaging analysis in neurorehabilitation outcome research

Although most neurological patients that enter a rehabilitation treatment program have had either a computed tomography (CT) or magnetic resonance imaging (MRI) scan, the utilization of neuroimaging in rehabilitation has been limited. However, a number of new MRI methods for image analysis hold great promise to better inform the neurorehabilitation clinician. The current review provides a foundation in neuroimaging fundamentals for neurorehabilitation specialists and examines the progress in using such techniques as quantitative MRI analyses, diffusion tensor imaging (DTI) and functional MRI to better understand the neurologically impaired patient.

High‐Level Gait Disorder: Associations with Specific White Matter Changes Observed on Advanced Diffusion Imaging

High-level gait disorder (HLGD) is a debilitating disorder causing mobility decline in the elderly. Although its clinical characteristics are well described, its anatomical and pathophysiological underpinnings are poorly understood. This study examined the anatomical distribution of white matter (WM) changes in patients with mild to moderate HLGD of the cautious/disequilibrium type, using advanced magnetic resonance imaging (MRI) methods. Thirteen patients with HLGD, 9 elderly and 13 middle-aged healthy controls were scanned using diffusion tensor imaging, Q-space imaging, and conventional MRI. The regions of significant differences between the HLGD group and the elderly control group were defined, and the mean fractional anisotropy and displacement values of these areas were extracted. The HLGD patients had lower fractional anisotropy and higher displacement values in regions related to the motor system, including those along the corticospinal tract and the superior cerebellar peduncles, as well as in cognitive and affective-related areas, including the anterior limbs of the internal capsule and the genu of the corpus callosum. The anatomical distribution associated with HLGD of the cautious/disequilibrium type involves WM pathways that convey motor-related, cognitive and affective-related functions. The underlying pathological process leading to these changes most probably includes demyelination.

Does the use of hormonal contraceptives cause microstructural changes in cerebral white matter? Preliminary results of a DTI and tractography study

To evaluate the effect of monophasic combined oral contraceptive pill (COCP) and menstrual cycle phase in healthy young women on white matter (WM) organization using diffusion tensor imaging (DTI). Thirty young women were included in the study; 15 women used COCP and 15 women had a natural cycle. All subjects underwent DTI magnetic resonance imaging during the follicular and luteal phase of their cycle, or in different COCP cycle phases. DTI parameters were obtained in different WM structures by performing diffusion tensor fibre tractography. Fractional anisotropy and mean diffusivity were calculated for different WM structures. Hormonal plasma concentrations were measured in peripheral venous blood samples and correlated with the DTI findings. We found a significant difference in mean diffusivity in the fornix between the COCP and the natural cycle group. Mean diffusivity values in the fornix were negatively correlated with luteinizing hormone and estradiol blood concentrations. An important part in the limbic system, the fornix, regulates emotional processes. Differences in diffusion parameters in the fornix may contribute to behavioural alternations related to COCP use. This finding also suggests that the use of oral contraceptives needs to be taken into account when designing DTI group studies.

The relationship between delirium duration, white matter integrity, and cognitive impairment in intensive care unit survivors as determined by diffusion tensor imaging: the VISIONS prospective cohort magnetic resonance imaging study*.

Evidence is emerging that delirium duration is a predictor of long-term cognitive impairment in intensive care unit survivors. Relationships between 1) delirium duration and brain white matter integrity, and 2) white matter integrity and long-term cognitive impairment are poorly understood and could be explored using magnetic resonance imaging. A two-center, prospective cohort study incorporating delirium monitoring, neuroimaging, and cognitive testing in intensive care unit survivors. Delirium was evaluated with the Confusion Assessment Method for the Intensive Care Unit and cognitive outcomes were tested at 3 and 12-month follow-up. Following the intensive care unit stay, fractional anisotropy, a measure of white matter integrity, was calculated quantitatively using diffusion tensor imaging with a 3-T magnetic resonance imaging scanner at hospital discharge and 3-month follow-up. We examined associations between 1) delirium duration and fractional anisotropy and 2) fractional anisotropy and cognitive outcomes using linear regression adjusted for age and sepsis. A total of 47 patients with a median age of 50 yrs completed the diffusion tensor imaging-magnetic resonance imaging protocol. Greater duration of delirium (3 vs. 0 days) was associated with lower fractional anisotropy (i.e., reduced fractional anisotropy = white matter disruption) in the genu (-0.02; p = .04) and splenium (-0.01; p = .02) of the corpus callosum and anterior limb of the internal capsule (-0.02; p =.01) at hospital discharge. These associations persisted at 3 months for the genu (-0.02; p =.02) and splenium (-0.01; p = .004). Lower fractional anisotropy in the anterior limb of internal capsule at discharge and in genu of corpus callosum at three months was associated with worse cognitive scores at 3 and 12 months. In this pilot investigation, delirium duration in the intensive care unit was associated with white matter disruption at both discharge and 3 months. Similarly, white matter disruption was associated with worse cognitive scores up to 12 months later. This hypothesis-generating investigation may help design future studies to explore these complex relationships in greater depth.

Adults with attention-deficit/hyperactivity disorder — A diffusion-tensor imaging study of the corpus callosum

The objective of the present study was to investigate the microstructure and the macrostructure of the corpus callosum (CC) in adults with Attention-Deficit/Hyperactivity Disorder (ADHD) by means of magnetic resonance imaging (MRI). Twenty-nine participants with ADHD and 37 controls were included from the Norwegian ADHD project in Bergen. We measured the fractional anisotropy (FA) values, as well as the size of different subdivisions of the CC, using diffusion tensor imaging (DTI) and anatomical MRI. The isthmus/splenium part of the CC in the ADHD group showed reduced FA values compared to the control group, whereas the size of the CC did not differ across groups. Our findings thus demonstrate a divergence between microstructural and macrostructural measures in the CC of adults with ADHD. This contrasts with findings in children demonstrating callosal abnormalities in both microstructure and macrostructure. Our results may indicate that adults with ADHD in part have succeeded in passing by an earlier developmental delay of the CC, resulting in a normalization of callosal macrostructure into adulthood. However, microstructural differences are still present in adults, which may point to an abnormal lateralization in adults with ADHD, or could be a sign of a persisting impairment.

Diffusion abnormality maps in demyelinating disease: Correlations with clinical scores

Magnetic resonance imaging (MRI) has been explored as a noninvasive tool to assess pathology in multiple sclerosis (MS) patients. However, the correlation between classical MRI measures and physical disability is modest in MS. The diffusion tensor imaging (DTI) MRI technique holds particular promise in this regard. The present study shows brain regions where FA and individual diffusivities abnormalities are present and check their correlations with physical disability clinical scores. Eight patients and 12 matched healthy controls were recruited. The Multiple Sclerosis Functional Composite was administered. For MR-DTI acquisitions, a Genesis Signa 1.5 T MR system, an EP/SE scanning sequence, 25 gradient directions were used. Tract Based Spatial Statistics (TBSS) group comparisons showed reduced FA and increased individual diffusivities in several brain regions in patients. Significant correlations were found between FA and: EDSS, 9-HPT(NON)DOM and 25 FW score; between λ2 and: P100 (r&l), 9-HPT(NON)DOM and 25 FW; between λ3 and: 9-HPT(NON)DOM and 25 FW score. Fractional anisotropy and individual radial diffusivities proved to be important markers of motor disabilities in MS patients when the disease duration mean and the disability scores values range are relatively high.

Measures of spinal canal stenosis and relationship to spinal cord structure in patients with cervical spondylosis

Spinal canal stenosis is often measured on anatomical magnetic resonance imaging (MRI) to estimate the degree of spinal cord compression. This study examined whether two quantitative measures of spinal canal stenosis taken from anatomical MRI are related to spinal cord white-matter integrity in patients with cervical spondylosis measured by diffusion tensor imaging (DTI). DTI and T2-weighted MRI of the cervical spinal cord were performed in 15 patients with cervical spondylosis and ten healthy control subjects of similar age. Severity of stenosis was calculated using Pavlov's ratio and the space-available-for-cord (SAC) technique. Patients had significantly lower Pavlov's ratios and SAC (C2-C3, C4-C5 and C6-C7), lower fractional anisotropy (FA; C2-C3 and C4-C5) and higher radial diffusivity (C2-C3, C4-C5 and C6-C7) than the controls. In patients, only Pavlov's ratio correlated with mean FA (R=0.66, P=0.008). Variations in Pavlov's ratio and FA also showed a similar pattern across cervical levels. Pavlov's ratio is a better predictor of spinal cord integrity than the SAC and, therefore, may be more relevant clinically for the evaluation of stenosis in patients with cervical spondylosis.

Diffusion Tensor Imaging of the Cerebellum and Eyeblink Conditioning in Fetal Alcohol Spectrum Disorder

Prenatal alcohol exposure is related to a wide range of neurocognitive effects. Eyeblink conditioning (EBC), which involves temporal pairing of a conditioned with an unconditioned stimulus, has been shown to be a potential biomarker of fetal alcohol exposure. A growing body of evidence suggests that white matter may be a specific target of alcohol teratogenesis, and the neural circuitry underlying EBC is known to involve the cerebellar peduncles. Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that has proven useful for assessing central nervous system white matter integrity. This study used DTI to examine the degree to which the fetal alcohol-related deficit in EBC may be mediated by structural impairment in the cerebellar peduncles. Thirteen children with fetal alcohol spectrum disorder (FASD) and 12 matched controls were scanned using DTI and structural MRI sequences. The DTI data were processed using a voxelwise technique, and the structural data were used for volumetric analyses. Prenatal alcohol exposure group and EBC performance were examined in relation to brain volumes and outputs from the DTI analysis. Fractional anisotropy (FA) and perpendicular diffusivity group differences between alcohol-exposed and nonexposed children were identified in the left middle cerebellar peduncle. Alcohol exposure correlated with lower FA and greater perpendicular diffusivity in this region, and these correlations remained significant even after controlling for total brain and cerebellar volumes. Conversely, trace conditioning performance was related to higher FA and lower perpendicular diffusivity in the left middle peduncle. The effect of prenatal alcohol exposure on trace conditioning was partially mediated by lower FA in this region. This study extends recent findings that have used DTI to reveal microstructural deficits in white matter in children with FASD. This is the first DTI study to demonstrate mediation of a fetal alcohol-related effect on neuropsychological function by deficits in white matter integrity.

Changes of Brain Structure and Function in ADHD Children

To explore the changes of brain structure and function in attention-deficit/hyperactivity disorder (ADHD), fifteen ADHD patients (inattention subtype) and 15 normal control participants were recruited, the brain structure and function of these subjects were investigated by combining structural magnetic resonance imaging (MRI), diffusion tensor imaging and resting-state functional MRI. The results showed that ADHD patients had a significant decrease in the volume of the white matter (P=0.04), and a trend toward decreased volume of brain structures except for the putamen and globus pallidus. The visualization of statistical difference maps of the cortical thickness showed that ADHD patients had focal thinning in bilateral frontal regions and the right cingulate cortex (P<0.05 uncorrected, except for a cluster threshold of 10 voxels). Statistical analysis of the FA maps revealed that ADHD patients had significantly decreased FA in the forceps minor, the internal capsule, the corona radiata, the splenium of the corpus callosum, and the bilateral basal ganglia (P<0.05 uncorrected as above). ADHD patients had significantly decreased functional connectivity in the anterior cingulate cortex, posterior cingulate cortex, lateral prefrontal cortex, left precuneus and thalamus, but increased functional connectivity in bilateral posterior medial frontal cortex in the default mode network (P<0.05 uncorrected as above). Our results provide new insights into the changes of the brain structure and function in ADHD, which suggests that alterations in the brain structural and functional connectivity might implicate the pathophysiology of ADHD.