Discriminant analysis using MRI asymmetry indices and cognitive scores of women with temporal lobe epilepsy or schizophrenia.

PURPOSE: This study aims to assess the diagnostic power of brain asymmetry indices and neuropsychological tests for differentiating mesial temporal lobe epilepsy (MTLE) and schizophrenia (SCZ). METHODS: We studied a total of 39 women including 13 MTLE, 13 SCZ, and 13 healthy individuals (HC). A neuropsychological test battery (NPT) was administered and scored by an experienced neuropsychologist, and NeuroQuant (CorTechs Labs Inc., San Diego, California) software was used to calculate brain asymmetry indices (ASI) for 71 different anatomical regions of all participants based on their 3D T1 MR imaging scans. RESULTS: Asymmetry indices measured from 10 regions showed statistically significant differences between the three groups. In this study, a multi-class linear discriminant analysis (LDA) model was built based on a total of fifteen variables composed of the most five significantly informative NPT scores and ten significant asymmetry indices, and the model achieved an accuracy of 87.2%. In pairwise classification, the accuracy for distinguishing MTLE from either SCZ or HC was 94.8%, while the accuracy for distinguishing SCZ from either MTLE or HC was 92.3%. CONCLUSION: The ability to differentiate MTLE from SCZ using neuroradiological and neuropsychological biomarkers, even within a limited patient cohort, could make a substantial contribution to research in larger patient groups using different machine learning techniques.

Neuroquantification enhances the radiological evaluation of term neonatal hypoxic-ischaemic cerebral injuries.

Background: Injury patterns in hypoxic-ischaemic brain injury (HIBI) are well recognised but there are few studies evaluating cerebral injury using neuroquantification models. Objectives: Quantification of brain volumes in a group of patients with clinically determined cerebral palsy. Method: In this retrospective study, 297 children with cerebral palsy were imaged for suspected HIBI with analysis of various cerebral substrates. Of these, 96 children over the age of 3 years with a clinical diagnosis of cerebral palsy and abnormal MRI findings underwent volumetric analyses using the NeuroQuant® software solution. The spectrum of volumetric changes and the differences between the various subtypes (and individual subgroups) of HIBI were compared. Results: Compared with the available normative NeuroQuant® database, the average intracranial volume was reduced to the 1st percentile in all patient groups (p < 0.001). Statistically significant differences were observed among the types and subgroups of HIBI. Further substrate volume reductions were identified and described involving the thalami, brainstem, hippocampi, putamina and amygdala. The combined volumes of five regions of interest (frontal pole, putamen, hippocampus, brainstem and paracentral lobule) were consistently reduced in the Rolandic basal ganglia-thalamus (RBGT) subtype. Conclusion: This study determined a quantifiable reduction of intracranial volume in all subtypes of HIBI and predictable selective cerebral substrate volume reduction in subtypes and subgroups. In the RBGT subtype, a key combination of five substrate injuries was consistently noted, and thalamic, occipital lobe and brainstem volume reduction was also significant when compared to the watershed subtype. Contribution: This study demonstrates the value of integrating an artificial intelligence programme into the radiologists' armamentarium serving to quantify brain injuries more accurately in HIBI. Going forward this will be an inevitable evolution of daily radiology practice in many fields of medicine, and it would be beneficial for radiologists to embrace these technological innovations.

Identification of metabolic correlates of mild cognitive impairment in Parkinson's disease using magnetic resonance spectroscopic imaging and machine learning.

OBJECTIVE: To investigate metabolic changes of mild cognitive impairment in Parkinson's disease (PD-MCI) using proton magnetic resonance spectroscopic imaging (1H-MRSI). METHODS: Sixteen healthy controls (HC), 26 cognitively normal Parkinson's disease (PD-CN) patients, and 34 PD-MCI patients were scanned in this prospective study. Neuropsychological tests were performed, and three-dimensional 1H-MRSI was obtained at 3 T. Metabolic parameters and neuropsychological test scores were compared between PD-MCI, PD-CN, and HC. The correlations between neuropsychological test scores and metabolic intensities were also assessed. Supervised machine learning algorithms were applied to classify HC, PD-CN, and PD-MCI groups based on metabolite levels. RESULTS: PD-MCI had a lower corrected total N-acetylaspartate over total creatine ratio (tNAA/tCr) in the right precentral gyrus, corresponding to the sensorimotor network (p = 0.01), and a lower tNAA over myoinositol ratio (tNAA/mI) at a part of the default mode network, corresponding to the retrosplenial cortex (p = 0.04) than PD-CN. The HC and PD-MCI patients were classified with an accuracy of 86.4% (sensitivity = 72.7% and specificity = 81.8%) using bagged trees. CONCLUSION: 1H-MRSI revealed metabolic changes in the default mode, ventral attention/salience, and sensorimotor networks of PD-MCI patients, which could be summarized mainly as 'posterior cortical metabolic changes' related with cognitive dysfunction.

A Macro-Structural Dispersion Characteristic of Brain White Matter and Its Application to Bipolar Disorder.

OBJECTIVE: Our goal is to find distinct characteristics of brain white matter in bipolar disorder, of which the development of diagnostic imaging measures is necessary for early diagnosis and prospective studies. METHODS: Given a tractogram dataset which is a dense set of white matter fiber pathways of the whole brain obtained from diffusion magnetic resonance imaging, we propose to compute a global measure for a voxel from the dispersion statistics of a set of fibers which indicates the complexity of the white matter voxel not locally but at macroscopic scales. RESULTS: Our findings demonstrate that macro-structural dispersion information is significant for discrimination of the bipolar patients from the healthy controls, particularly in the frontally associative bundles such as cingulum and inferior occipito-frontal fascicles. CONCLUSION: The proposed measure is as informative as the local diffusion measures for the detection of changes in the white matter regions. SIGNIFICANCE: Our findings show that the proposed measure is a potential diagnostic imaging marker in bipolar disorder and the proposed novel dispersion map of the brain could be used for other neurological applications.

The cerebral blood flow deficits in Parkinson's disease with mild cognitive impairment using arterial spin labeling MRI.

Parkinson's disease (PD) with mild cognitive impairment (PD-MCI) is currently diagnosed based on an arbitrarily predefined standard deviation of neuropsychological test scores, and more objective biomarkers for PD-MCI diagnosis are needed. The purpose of this study was to define possible brain perfusion-based biomarkers of not only mild cognitive impairment, but also risky gene carriers in PD using arterial spin labeling magnetic resonance imaging (ASL-MRI). Fifteen healthy controls (HC), 26 cognitively normal PD (PD-CN), and 27 PD-MCI subjects participated in this study. ASL-MRI data were acquired by signal targeting with alternating radio-frequency labeling with Look-Locker sequence at 3 T. Single nucleotide polymorphism genotyping for rs9468 [microtubule-associated protein tau (MAPT) H1/H1 versus H1/H2 haplotype] was performed using a Stratagene Mx3005p real-time polymerase chain-reaction system (Agilent Technologies, USA). There were 15 subjects with MAPT H1/H1 and 11 subjects with MAPT H1/H2 within PD-MCI, and 33 subjects with MAPT H1/H1 and 19 subjects with MAPT H1/H2 within all PD. Voxel-wise differences of cerebral blood flow (CBF) values between HC, PD-CN and PD-MCI were assessed by one-way analysis of variance followed by pairwise post hoc comparisons. Further, the subgroup of PD patients carrying the risky MAPT H1/H1 haplotype was compared with noncarriers (MAPT H1/H2 haplotype) in terms of CBF by a two-sample t test. A pattern that could be summarized as "posterior hypoperfusion" (PH) differentiated the PD-MCI group from the HC group with an accuracy of 92.6% (sensitivity = 93%, specificity = 93%). Additionally, the PD patients with MAPT H1/H1 haplotype had decreased perfusion than the ones with H1/H2 haplotype at the posterior areas of the visual network (VN), default mode network (DMN), and dorsal attention network (DAN). The PH-type pattern in ASL-MRI could be employed as a biomarker of both current cognitive impairment and future cognitive decline in PD.

Investigation of superior longitudinal fasciculus fiber complexity in recent onset psychosis.

BACKGROUND: Standard diffusion tensor imaging measures (e.g., fractional anisotropy; FA) are difficult to interpret in brain regions with crossing white-matter (WM) fibers. Diffusion spectrum imaging (DSI) can be used to resolve fiber crossing, but has been difficult to implement in studies of patients with psychosis given long scan times. METHODS: We used four fold accelerated compressed sensing to accelerate DSI acquisition to investigate the superior longitudinal fasciculus (SLF) in 27 (20M/7F) patients with recent onset psychosis and 23 (11M/12F) healthy volunteers. Dependent measures included the number of crossing fiber directions, multi directional anisotropy (MDA), which is a measure sensitive to the anisotropy of the underlying water diffusion in regions of crossing fibers, generalized FA (GFA) computed from the orientation distribution function, FA and tract volume. RESULTS: Patients demonstrated a greater number of crossing WM fibers, lower MDA, GFA and FA in the left SLF compared to healthy volunteers. Patients also demonstrated a reversal in the normal (R>L) asymmetry of crossing fiber directions in the SLF and a lack of normal (L>R) asymmetry in MDA, GFA and FA compared to healthy volunteers. Lower GFA correlated significantly (p<0.05) with worse overall neuropsychological functioning; posthoc tests revealed significant effects with verbal functioning and processing speed. CONCLUSIONS: Our findings provide the first in vivo evidence for abnormal crossing fibers within the SLF among individuals with psychosis and their functional correlates. A reversal in the normal pattern of WM asymmetry of crossing fibers in patients may be consistent with an aberrant neurodevelopmental process.

Differential medial temporal lobe morphometric predictors of item- and relational-encoded memories in healthy individuals and in individuals with mild cognitive impairment and Alzheimer's disease.

INTRODUCTION: Episodic memory processes are supported by different subregions of the medial temporal lobe (MTL). In contrast to a unitary model of memory recognition supported solely by the hippocampus, a current model suggests that item encoding engages perirhinal cortex, whereas relational encoding engages parahippocampal cortex and the hippocampus. However, this model has not been examined in the context of aging, neurodegeneration, and MTL morphometrics. METHODS: Forty-four healthy subjects (HSs) and 18 cognitively impaired subjects (nine mild cognitive impairment [MCI] and nine Alzheimer's disease [AD] patients) were assessed with the relational and item-specific encoding task (RISE) and underwent 3T magnetic resonance imaging. The RISE assessed the differential contribution of relational and item-specific memory. FreeSurfer was used to obtain measures of cortical thickness of MTL regions and hippocampus volume. RESULTS: Memory accuracies for both item and relational memory were significantly better in the HS group than in the MCI/AD group. In MCI/AD group, relational memory was disproportionately impaired. In HSs, hierarchical regressions demonstrated that memory was predicted by perirhinal thickness after item encoding, and by hippocampus volume after relational encoding (both at trend level) and significantly by parahippocampal thickness at associative recognition. The same brain morphometry profiles predicted memory accuracy in MCI/AD, although more robustly perirhinal thickness for item encoding (R2 = 0.31) and hippocampal volume and parahippocampal thickness for relational encoding (R2 = 0.31). DISCUSSION: Our results supported a model of episodic memory in which item-specific encoding was associated with greater perirhinal cortical thickness, while relational encoding was associated with parahippocampal thickness and hippocampus volume. We identified these relationships not only in HSs but also in individuals with MCI and AD. In the subjects with cognitive impairment, reductions in hippocampal volume and impairments in relational memory were especially prominent.

Parkinson's disease-related network topographies characterized with resting state functional MRI.

Spatial covariance mapping can be used to identify and measure the activity of disease-related functional brain networks. While this approach has been widely used in the analysis of cerebral blood flow and metabolic PET scans, it is not clear whether it can be reliably applied to resting state functional MRI (rs-fMRI) data. In this study, we present a novel method based on independent component analysis (ICA) to characterize specific network topographies associated with Parkinson's disease (PD). Using rs-fMRI data from PD and healthy subjects, we used ICA with bootstrap resampling to identify a PD-related pattern that reliably discriminated the two groups. This topography, termed rs-MRI PD-related pattern (fPDRP), was similar to previously characterized disease-related patterns identified using metabolic PET imaging. Following pattern identification, we validated the fPDRP by computing its expression in rs-fMRI testing data on a prospective case basis. Indeed, significant increases in fPDRP expression were found in separate sets of PD and control subjects. In addition to providing a similar degree of group separation as PET, fPDRP values correlated with motor disability and declined toward normal with levodopa administration. Finally, we used this approach in conjunction with neuropsychological performance measures to identify a separate PD cognition-related pattern in the patients. This pattern, termed rs-fMRI PD cognition-related pattern (fPDCP), was topographically similar to its PET-derived counterpart. Subject scores for the fPDCP correlated with executive function in both training and testing data. These findings suggest that ICA can be used in conjunction with bootstrap resampling to identify and validate stable disease-related network topographies in rs-fMRI. Hum Brain Mapp 38:617-630, 2017. © 2016 Wiley Periodicals, Inc.

The visual perception of natural motion: abnormal task-related neural activity in DYT1 dystonia.

Although primary dystonia is defined by its characteristic motor manifestations, non-motor signs and symptoms have increasingly been recognized in this disorder. Recent neuroimaging studies have related the motor features of primary dystonia to connectivity changes in cerebello-thalamo-cortical pathways. It is not known, however, whether the non-motor manifestations of the disorder are associated with similar circuit abnormalities. To explore this possibility, we used functional magnetic resonance imaging to study primary dystonia and healthy volunteer subjects while they performed a motion perception task in which elliptical target trajectories were visually tracked on a computer screen. Prior functional magnetic resonance imaging studies of healthy subjects performing this task have revealed selective activation of motor regions during the perception of 'natural' versus 'unnatural' motion (defined respectively as trajectories with kinematic properties that either comply with or violate the two-thirds power law of motion). Several regions with significant connectivity changes in primary dystonia were situated in proximity to normal motion perception pathways, suggesting that abnormalities of these circuits may also be present in this disorder. To determine whether activation responses to natural versus unnatural motion in primary dystonia differ from normal, we used functional magnetic resonance imaging to study 10 DYT1 dystonia and 10 healthy control subjects at rest and during the perception of 'natural' and 'unnatural' motion. Both groups exhibited significant activation changes across perceptual conditions in the cerebellum, pons, and subthalamic nucleus. The two groups differed, however, in their responses to 'natural' versus 'unnatural' motion in these regions. In healthy subjects, regional activation was greater during the perception of natural (versus unnatural) motion (P < 0.05). By contrast, in DYT1 dystonia subjects, activation was relatively greater during the perception of unnatural (versus natural) motion (P < 0.01). To explore the microstructural basis for these functional changes, the regions with significant interaction effects (i.e. those with group differences in activation across perceptual conditions) were used as seeds for tractographic analysis of diffusion tensor imaging scans acquired in the same subjects. Fibre pathways specifically connecting each of the significant functional magnetic resonance imaging clusters to the cerebellum were reconstructed. Of the various reconstructed pathways that were analysed, the ponto-cerebellar projection alone differed between groups, with reduced fibre integrity in dystonia (P < 0.001). In aggregate, the findings suggest that the normal pattern of brain activation in response to motion perception is disrupted in DYT1 dystonia. Thus, it is unlikely that the circuit changes that underlie this disorder are limited to primary sensorimotor pathways.

18FDG-microPET and MR DTI findings in Tor1a+/- heterozygous knock-out mice.

TorsinA is an important protein in brain development, and plays a role in the regulation of neurite outgrowth and synaptic function. Patients with the most common form of genetic dystonia carry a mutation (DYT1) in one copy of the Tor1a gene, a 3-bp deletion, causing removal of a single glutamic acid from torsinA. Previous imaging studies have shown that abnormal cerebellar metabolism and damaged cerebello-thalamo-cortical pathway contribute to the pathophysiology of DYT1 dystonia. However, how a mutation in one copy of the Tor1a gene causes these abnormalities is not known. We studied Tor1a heterozygous knock-out mice in vivo with FDG-PET and ex vivo with diffusion tensor imaging. We found metabolic abnormalities in cerebellum, caudate-putamen, globus pallidus, sensorimotor cortex and subthalamic nucleus. We also found that FA was increased in caudate-putamen, sensorimotor cortex and brainstem. We compared our findings with a previous imaging study of the Tor1a knock-in mice. Our study suggested that having only one normal copy of Tor1a gene may be responsible for the metabolic abnormalities observed; having a copy of mutant Tor1a, on the other hand, may be responsible for white matter pathway damages seen in DYT1 dystonia subjects.

Thalamocortical Connectivity Correlates with Phenotypic Variability in Dystonia.

Dystonia is a brain disorder characterized by abnormal involuntary movements without defining neuropathological changes. The disease is often inherited as an autosomal-dominant trait with incomplete penetrance. Individuals with dystonia, whether inherited or sporadic, exhibit striking phenotypic variability, with marked differences in the somatic distribution and severity of clinical manifestations. In the current study, we used magnetic resonance diffusion tensor imaging to identify microstructural changes associated with specific limb manifestations. Functional MRI was used to localize specific limb regions within the somatosensory cortex. Microstructural integrity was preserved when assessed in subrolandic white matter regions somatotopically related to the clinically involved limbs, but was reduced in regions linked to clinically uninvolved (asymptomatic) body areas. Clinical manifestations were greatest in subjects with relatively intact microstructure in somatotopically relevant white matter regions. Tractography revealed significant phenotype-related differences in the visualized thalamocortical tracts while corticostriatal and corticospinal pathways did not differ between groups. Cerebellothalamic microstructural abnormalities were also seen in the dystonia subjects, but these changes were associated with genotype, rather than with phenotypic variation. The findings suggest that the thalamocortical motor system is a major determinant of dystonia phenotype. This pathway may represent a novel therapeutic target for individuals with refractory limb dystonia.

Regional brain metabolism in a murine systemic lupus erythematosus model.

Systemic lupus erythematosus (SLE) is characterized by multiorgan inflammation, neuropsychiatric disorders (NPSLE), and anti-nuclear antibodies. We previously identified a subset of anti-DNA antibodies (DNRAb) cross-reactive with the N-methyl-D-aspartate receptor, present in 30% to 40% of patients, able to enhance excitatory post-synaptic potentials and trigger neuronal apoptosis. DNRAb+ mice exhibit memory impairment or altered fear response, depending on whether the antibody penetrates the hippocampus or amygdala. Here, we used 18F-fluorodeoxyglucose (FDG) microPET to plot changes in brain metabolism after regional blood-brain barrier (BBB) breach. In DNRAb+ mice, metabolism declined at the site of BBB breach in the first 2 weeks and increased over the next 2 weeks. In contrast, DNRAb- mice exhibited metabolic increases in these regions over the 4 weeks after the insult. Memory impairment was present in DNRAb+ animals with hippocampal BBB breach and altered fear conditioning in DNRAb+ mice with amygdala BBB breach. In DNRAb+ mice, we observed an inverse relationship between neuron number and regional metabolism, while a positive correlation was observed in DNRAb- mice. These findings suggest that local metabolic alterations in this model take place through different mechanisms with distinct time courses, with important implications for the interpretation of imaging data in SLE subjects.

Independent component analysis of resting state activity in pediatric obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is an often severely disabling illness with onset generally in childhood or adolescence. Little is known, however, regarding the pattern of brain resting state activity in OCD early in the course of illness. We therefore examined differences in brain resting state activity in patients with pediatric OCD compared with healthy volunteers and their clinical correlates. Twenty-three pediatric OCD patients and 23 healthy volunteers (age range 9-17), matched for sex, age, handedness, and IQ completed a resting state functional magnetic resonance imaging exam at 3T. Patients completed the Children's Yale Brown Obsessive Scale. Data were decomposed into 36 functional networks using spatial group independent component analysis (ICA) and logistic regression was used to identify the components that yielded maximum group separation. Using ICA we identified three components that maximally separated the groups: a middle frontal/dorsal anterior cingulate network, an anterior/posterior cingulate network, and a visual network yielding an overall group classification of 76.1% (sensitivity = 78.3% and specificity = 73.9%). Independent component expression scores were significantly higher in patients compared with healthy volunteers in the middle frontal/dorsal anterior cingulate and the anterior/posterior cingulate networks, but lower in patients within the visual network. Higher expression scores in the anterior/posterior cingulate network correlated with greater severity of compulsions among patients. These findings implicate resting state fMRI abnormalities within the cingulate cortex and related control regions in the pathogenesis and phenomenology of OCD early in the course of the disorder and prior to extensive pharmacologic intervention.

APOE genotype modulates proton magnetic resonance spectroscopy metabolites in the aging brain.

BACKGROUND: Proton magnetic resonance spectroscopy ((1)H-MRS) studies on healthy aging have reported inconsistent findings and have not systematically taken into account the possible modulatory effect of APOE genotype. We aimed to quantify brain metabolite changes in healthy subjects in relation to age and the presence of the APOE E4 genetic risk factor for Alzheimer's disease. Additionally, we examined these measures in relation to cognition. METHODS: We studied a cohort of 112 normal adults between 50 and 86 years old who were genotyped for APOE genetic polymorphism. Measurements of (1)H-MRS metabolites were obtained in the posterior cingulate and precuneus region. Measures of general cognitive functioning, memory, executive function, semantic fluency, and speed of processing were also obtained. RESULTS: General linear model analysis demonstrated that older APOE E4 carriers had significantly higher choline/creatine and myo-inositol/creatine ratios than APOE E3 homozygotes. Structural equation modeling resulted in a model with an excellent goodness of fit and in which the APOE × age interaction and APOE status each had a significant effect on (1)H-MRS metabolites (choline/creatine and myo-inositol/creatine). Furthermore, the APOE × age variable modulation of cognition was mediated by (1)H-MRS metabolites. CONCLUSIONS: In a healthy aging normal population, choline/creatine and myo-inositol/creatine ratios were significantly increased in APOE E4 carriers, suggesting the presence of neuroinflammatory processes and greater membrane turnover in older carriers. Structural equation modeling analysis confirmed these possible neurodegenerative markers and also indicated the mediator role of these metabolites on cognitive performance among older APOE E4 carriers.

Cognitive dysfunction in antiphospholipid antibody (aPL)-negative systemic lupus erythematosus (SLE) versus aPL-positive non-SLE patients.

OBJECTIVES: The aim of this study was to compare the cognitive function of antiphospholipid antibody (aPL)-negative systemic lupus erythematosus (SLE) and aPL-positive non-SLE patients. METHODS: Twenty aPL-negative SLE and 20 aPL-positive non-SLE female patients with no history of overt neuropsychiatric manifestations took standardised cognitive tests of learning and memory, attention and working memory, executive functions, verbal fluency, visuoconstruction, and motor function. The primary outcome measure was an established global cognitive impairment index (CII). Cranial magnetic resonance imaging (MRI) was also obtained on all patients. RESULTS: Twelve of 20 (60%) of the SLE and 8/20 (40%) of the aPL-positive patients had global cognitive impairment on CII; there were no group differences on CII or on individual measures. Cognitive impairment was not associated with duration of disease, level of disease activity, or prednisone use. No correlations were found between clinical disease factors and cognitive impairment, and neither group showed an association between incidental or major MRI abnormalities and cognitive dysfunction. CONCLUSIONS: Both aPL-negative SLE and aPL-positive non-SLE patients, without other overt neuropsychiatric disease, demonstrated high levels of cognitive impairment. No clinical, serologic, or radiologic characteristics were associated with cognitive impairment. Cognitive dysfunction is common in APS and in SLE, but its mechanisms remain unknown.

White matter abnormalities in pediatric obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a prevalent and often severely disabling illness with onset generally in childhood or adolescence. Although white matter deficits have been implicated in the neurobiology of OCD, few studies have been conducted in pediatric patients when the brain is still developing and have examined their functional correlates. In this study, 23 pediatric OCD patients and 23 healthy volunteers, between the ages of 9 and 17 years, matched for sex, age, handedness, and IQ, received a diffusion tensor imaging exam on a 3T GE system and a brief neuropsychological battery tapping executive functions. Patient symptom severity was assessed using the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). Patients with OCD exhibited significantly greater fractional anisotropy compared to matched controls in the left dorsal cingulum bundle, splenium of the corpus callosum, right corticospinal tract, and left inferior fronto-occipital fasciculus. There were no regions of significantly lower fractional anisotropy in patients compared to controls. Higher fractional anisotropy in the splenium was significantly correlated with greater obsession severity on the CY-BOCS in the subgroup of psychotropic drug-naïve patients. Among patients, there was a significant association between greater fractional anisotropy in the dorsal cingulum bundle and better performance on measures of response inhibition and cognitive control. The overall findings suggest a pattern of greater directional coherence of white matter tracts in OCD very early in the course of illness, which may serve a compensatory mechanism, at least for response inhibition functions typically subserved by the cingulum bundle.

Diffusion tensor imaging in carpal tunnel syndrome.

PURPOSE: We aimed to investigate the efficacy of diffusion tensor imaging in the diagnosis of carpal tunnel syndrome and to obtain a quantitative parameter that may contribute to the diagnosis. MATERIALS AND METHODS: The median nerves in 57 wrists of 38 patients diagnosed as carpal tunnel syndrome and 30 wrists of 24 normal subjects were prospectively evaluated with a 3T Philips scanner, using standard 8-channel SENSE head coil. Diffusion tensor imaging was performed using spin echo-echo planar imaging. For anatomical reference, a T1-weighted sequence was acquired. Fractional anisotropy and apparent diffusion coefficient measurements were done focally at the carpal tunnel level and from whole median nerve. RESULTS: In carpal tunnel syndrome patients, both focal carpal tunnel and whole nerve measurements demonstrated statistically significantly lower fractional anisotropy values than normal subjects (P < 0.001). No statistically significant difference was observed in apparent diffusion coefficient measurements. The cut-off value obtained by receiver operator characteristics analysis was 0.554 for focal carpal tunnel fractional anisotropy (sensitivity, 80%; specificity, 80%) and 0.660 for whole nerve fractional anisotropy (sensitivity, 82%; specificity, 80%) measurement. CONCLUSION: Diffusion tensor imaging may contribute to the diagnosis of carpal tunnel syndrome on the basis of fractional anisotropy measurements.

Differences in regional brain activation patterns assessed by functional magnetic resonance imaging in patients with systemic lupus erythematosus stratified by disease duration.

The mediators of tissue damage in systemic lupus erythematosus (SLE) such as antibodies, cytokines and activated immune cells have direct access to most organs in the body but must penetrate the blood-brain barrier (BBB) to gain access to brain tissue. We hypothesized that compromise of the BBB occurs episodically such that the brain will acquire tissue damage slowly and not at the same rate as other organs. On the basis of these assumptions, we wished to determine if duration of disease correlated with brain injury, as measured with functional magnetic resonance imaging (fMRI), and if this was independent of degree of tissue damage in other organs. We investigated differences in brain activation patterns using fMRI in 13 SLE patients stratified by disease duration of ≤2 years (short-term [ST]) or ≥10 years (long-term [LT]). Two fMRI paradigms were selected to measure working memory and emotional response (fearful faces task). Performance in the working memory task was significantly better in the ST group for one and two shape recall; however, both groups did poorly with three shape recall. Imaging studies demonstrated significantly increased cortical activation in the ST group in regions associated with cognition during the two shape retention phase of the working memory task (P < 0.001) and increased amygdala (P < 0.05) and superior parietal (P < 0.01) activation in response to the fearful faces paradigm. In conclusion, analysis of activation patterns stratified by performance accuracy, differences in co-morbid disease, corticosteroid doses or disease activity suggests that these observed differences are attributable to SLE effects on the central nervous system exclusive of vascular disease or other confounding influences. Our hypothesis is further supported by the lack of correlation between regional brain abnormalities on fMRI and the Systemic Lupus International Collaborating Clinics (SLICC) damage index.

Cerebellothalamocortical pathway abnormalities in torsinA DYT1 knock-in mice.

The factors that determine symptom penetrance in inherited disease are poorly understood. Increasingly, magnetic resonance diffusion tensor imaging (DTI) and PET are used to separate alterations in brain structure and function that are linked to disease symptomatology from those linked to gene carrier status. One example is DYT1 dystonia, a dominantly inherited movement disorder characterized by sustained muscle contractions, postures, and/or involuntary movements. This form of dystonia is caused by a 3-bp deletion (i.e., ΔE) in the TOR1A gene that encodes torsinA. Carriers of the DYT1 dystonia mutation, even if clinically nonpenetrant, exhibit abnormalities in cerebellothalamocortical (CbTC) motor pathways. However, observations in human gene carriers may be confounded by variability in genetic background and age. To address this problem, we implemented a unique multimodal imaging strategy in a congenic line of DYT1 mutant mice that contain the ΔE mutation in the endogenous mouse torsinA allele (i.e., DYT1 knock-in). Heterozygous knock-in mice and littermate controls underwent microPET followed by ex vivo high-field DTI and tractographic analysis. Mutant mice, which do not display abnormal movements, exhibited significant CbTC tract changes as well as abnormalities in brainstem regions linking cerebellar and basal ganglia motor circuits highly similar to those identified in human nonmanifesting gene carriers. Moreover, metabolic activity in the sensorimotor cortex of these animals was closely correlated with individual measures of CbTC pathway integrity. These findings further link a selective brain circuit abnormality to gene carrier status and demonstrate that DYT1 mutant torsinA has similar effects in mice and humans.