Voxel-based Diffusion Tensor Imaging Research Articles

Changes of Brain Structures and Psychological Characteristics in Predatory, Affective Violent and Nonviolent Offenders.

Purpose: Violent subjects were demonstrated to exhibit abnormal brain structures; however, the brain changes may be different between criminals committing affective (VA), predatory violence (VP), and non-violence (NV). Therefore, the purpose of this study was to compare the differences in brain structures and psychological characteristics between VA, VP, and NV offenders. Methods: Twenty male criminal subjects (7 VP; 6 VA; and 7 NV) offenders; and twenty age-matched male healthy non-criminals were enrolled in this study. All subjects received psychological assessments as well as magnetic resonance imaging scans of the brain. Analysis of variance (ANOVA) was performed to understand the differences among four groups with Bonferroni correction. The voxel-based morphometry and voxel-wise diffusion tensor imaging analyses were performed to compare the gray matter (GM) volume and white matter (WM) integrity between the groups. In significant regions, a Spearman correlation analysis was performed to understand the relationship between the brain changes and psychological scores. Results: The ANOVA analysis showed that AUDIT scores were significantly different among four groups, but no significant group difference was noted after Bonferroni correction. The imaging comparisons further demonstrated that the VP and NV offenders exhibited significant alterations of WM and GM tissues in the rectus and superior temporal gyrus, respectively. In addition, the VP offenders exhibited greater GM volumes than VA offenders in the right middle frontal gyrus, and NV offenders had greater GM volumes than VP offenders in the bilateral thalamus. Conclusion: We concluded that the VA, VP, and NV groups exhibited different degrees of alterations in GM and WM tissues in regions involved in emotion and cognition.

Pathomechanisms behind cognitive disorders following ruptured anterior communicating aneurysms: A diffusion tensor imaging study

IntroductionAfter the rupture of anterior communicating aneurysms, most patients experience debilitating cognitive disorders; and sometimes even without showing morphological anomaly on MRI examinations. Diffusion Tensor Imaging (DTI) may help understanding the pathomechanisms leading to such disorders in this subset of patients. MethodsAfter independent assessment, we constituted a population of patients with normal morphological imaging (ACOM group). Then, a case-control study comparing volumetric and voxel-based DTI parameters between the ACOM group and a control population was performed. All patients underwent the full imaging and neuropsychological assessments at 6 months after the aneurysm rupture. Results were considered significant when p<2.02.10−4. ResultsTwelve patients were included in the ACOM group: 75% had at least one disabled cognitive domain. Significant differences in DTI parameters of global white matter were noted (average Fractional Anisotropy: 0.915 [±0.05] in ACOM group versus 0.943 (±0.03); p = 1.10−5) and in frontal white matter tracts (superior fronto-occipital fasciculus and anterior parts of the corona radiata) as well as in the fornix. ConclusionCognitive disorders are under-estimated, and DTI confirmed that, even when conventional MRI examinations were normal, there were still signs of diffuse neuronal injuries that seemed to dominate in frontal areas, close to the site of rupture.

Callosal abnormalities, altered cortisol levels, and neurocognitive deficits associated with early maltreatment among adolescents: A voxel-based diffusion-tensor imaging study.

IntroductionNeuroimaging studies have shown callosal abnormalities among maltreated subjects, but little is known about the functional and neurobiological correlates of these supposed developmental alterations. The aim of this study was to investigate childhood maltreatment (CM), neurocognitive functioning, cortisol levels, and corpus callosum (CC) integrity among adolescents.MethodsOne hundred and seven subjects underwent magnetic resonance imaging (MRI) with voxel‐based diffusion‐tensor imaging (DTI) and the Crossed Finger Localization Test (CFLT). Psychopathology was investigated with the Schedule for Affective Disorders and Schizophrenia (K‐SADS‐PL); CM was detailed by the Childhood Trauma Questionnaire (CTQ), and salivary cortisol levels were measured by immunoassay.ResultsHigher levels of CM were associated with current lower CFLT scores, mainly in the CROSSED condition, involving interhemispheric communication of sensorimotor information (p < .05) and with reduced fractional anisotropy (FA) in the splenium of the CC (p < .01). Deficits in the CFLT were also associated with higher cortisol levels (p < .05).ConclusionThe association among CM, neuropsychological abnormalities, callosal microstructure alterations, and cortisol levels suggests an altered pattern of brain interhemispheric connectivity among maltreated adolescents. Further studies are needed to investigate the extent to which these sensorimotor deficits and abnormal cortisol levels may be possible mediators of negative neurodevelopmental trajectories and adult psychopathology.

Cognitive deficits and white matter abnormalities in never-treated first-episode schizophrenia

Cognitive impairment is viewed as a core symptom of schizophrenia (SCZ), but its pathophysiological mechanism remains unclear. White matter (WM) disruption is considered to be a central abnormality that may contribute to cognitive impairment in SCZ patients. However, few studies have addressed the association between cognition and WM integrity in never-treated first-episode (NTFE) patients with SCZ. In this study, we used the MATRICS Consensus Cognitive Battery (MCCB) to evaluate cognitive function in NTFE patients (n = 39) and healthy controls (n = 30), and associated it with whole-brain fractional anisotropy (FA) values obtained via voxel-based diffusion tensor imaging. We found that FA was lower in five brain areas of SCZ patients, including the cingulate gyrus, internal capsule, corpus callosum, cerebellum, and brainstem. Compared with the healthy control group, the MCCB’s total score and 8 out of 10 subscores were significantly lower in NTFE patients (all p < 0.001). Moreover, in patients but not healthy controls, the performance in the Trail Making Test was negatively correlated with the FA value in the left cingulate. Our findings provide evidence that WM disconnection is involved in some cognitive impairment in the early course of SCZ.

Sex-differential associations between cognitive impairments and white matter abnormalities in first episode and drug-naïve schizophrenia.

Previous evidence has suggested that schizophrenia patients may display sex differences in cognitive impairments and cognitive impairments are related to disrupted white matter (WM) microstructure. The current research aims to address the intriguing possibility for the sex-specific association between cognitive deficits and WM abnormalities in first-episode and drug-naïve schizophrenia. Cognitive performance on the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) was measured in 39 FEND patients (females:males=23:16) and 30 healthy controls (females:males=17:13), together with whole-brain WM fractional anisotropy (FA) values determined using voxel-based diffusion tensor imaging. Correlations between cognitive performance and FA values were assessed. Patients performed significantly worse than healthy controls in the total score and most of the subscores of MCCB. Female patients displayed better cognitive performance than male patients on the Trail Making A Test, the Hopkins Verbal Learning Test and the Spatial Span Test in the Wechsler Memory Scale. More importantly, sex-differential association between cognitive performance and FA values was found in patients, but not in healthy controls. In particular, FA values in the cerebellum were negatively correlated with the continuous performance and digital sequence scores in male patients but positively correlated with the performance on the Spatial Span Test in the Wechsler Memory Scale in female patients. These findings suggest sex-specific neurobiological substrates involved in cognitive deficits in early-onset schizophrenia and have important implications for differentially targeted interventions between males and females.

Cerebral Micro-Structural Changes in COVID-19 Patients: An MRI-Based Preliminary Study

Background: Increasing evidence supported the possible neuro-invasion potential of SARS-CoV-2. However, no studies were conducted to explore the existence of the structural changes in the neurological system after infection. We aimed to identify the existence of potential brain structural changes related to SARS-CoV-2. Methods: In this prospective study, diffusion tensor imaging (DTI) and 3D high-resolution T1WI sequences were acquired in 48 recovered COVID-19 patients (60.42% male; mean age=47.81 ± 19.51) and 31 age-matched healthy controls (29.03% male; age=43.45 ± 13.6). Registered fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivity (RD) were quantified for DTI, and a brain score system was introduced. Voxel-based Morphometry (VBM) and DTI metrics were compared using ANCOVA. Independent t-test and Spearman correlation were conducted to assess the relationships among imaging indices, brain scores and clinical information. Findings: COVID-19 patients had higher gray matter volumes (GMV) in hippocampus and Heschl’s gyrus, and higher white matter volumes (WMV) in corona radiata and tapetum. The left paracentral lobule was found to have significantly lower FA, higher MD, AD and RD values when compared with healthy controls. COVID-19 patients also had lower global MD and RD values, as well as lower brain scores of FA-GM, MD-GM, and MD-WM. MD values in the right corona radiata and external capsule were positively related to LDH level (r = 0.428, 0.417). Interpretation: Study findings reveal possible disruption to micro-structural and functional brain integrity in the recovery stages of COVID-19, suggesting neuro-invasion potential of SARS-CoV-2. Funding: This project was supported by Shanghai Natural Science Foundation (Grant No. 18ZR1405700), Youth Program of National Natural Science Foundation of China (Fund No. 81901697), Shanghai Sailing Program (Grant No. 18YF1403000), Shanghai Science and Technology Development (Fund No. 19511121204), Shanghai Municipal Science and Technology Major Project (No. 2018SHZDZX01) and ZJ Lab.Declaration of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethics Approval Statement: This was a prospective study, which was approved by the local ethics committee (No.20200616017) and written informed consent was obtained from each participant.

Cerebral Micro-Structural Changes in COVID-19 Patients - An MRI-based 3-month Follow-up Study.

BackgroundIncreasing evidence supported the possible neuro-invasion potential of SARS-CoV-2. However, no studies were conducted to explore the existence of the micro-structural changes in the central nervous system after infection. We aimed to identify the existence of potential brain micro-structural changes related to SARS-CoV-2.MethodsIn this prospective study, diffusion tensor imaging (DTI) and 3D high-resolution T1WI sequences were acquired in 60 recovered COVID-19 patients (56.67% male; age: 44.10 ± 16.00) and 39 age- and sex-matched non-COVID-19 controls (56.41% male; age: 45.88 ± 13.90). Registered fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were quantified for DTI, and an index score system was introduced. Regional volumes derived from Voxel-based Morphometry (VBM) and DTI metrics were compared using analysis of covariance (ANCOVA). Two sample t-test and Spearman correlation were conducted to assess the relationships among imaging indices, index scores and clinical information.FindingsIn this follow-up stage, neurological symptoms were presented in 55% COVID-19 patients. COVID-19 patients had statistically significantly higher bilateral gray matter volumes (GMV) in olfactory cortices, hippocampi, insulas, left Rolandic operculum, left Heschl's gyrus and right cingulate gyrus and a general decline of MD, AD, RD accompanied with an increase of FA in white matter, especially AD in the right CR, EC and SFF, and MD in SFF compared with non-COVID-19 volunteers (corrected p value <0.05). Global GMV, GMVs in left Rolandic operculum, right cingulate, bilateral hippocampi, left Heschl's gyrus, and Global MD of WM were found to correlate with memory loss (p value <0.05). GMVs in the right cingulate gyrus and left hippocampus were related to smell loss (p value <0.05). MD-GM score, global GMV, and GMV in right cingulate gyrus were correlated with LDH level (p value <0.05).InterpretationStudy findings revealed possible disruption to micro-structural and functional brain integrity in the recovery stages of COVID-19, suggesting the long-term consequences of SARS-CoV-2.FundingShanghai Natural Science Foundation, Youth Program of National Natural Science Foundation of China, Shanghai Sailing Program, Shanghai Science and Technology Development, Shanghai Municipal Science and Technology Major Project and ZJ Lab.

Voxel-based diffusion tensor imaging in focal epilepsies: comparative analyses of microstructural damage in pharmacoresponse of mesial temporal lobe epilepsy and frontal lobe epilepsy

The diffusion tensor image (DTI) is an MRI technique that allows noninvasive evaluation of white matter (WM). It describes the magnitude (mean diffusivity-MD) and directionality (fractional anisotropy-FA) of the movement of water molecules. Widespread WM changes measured by DTI has been described in focal epilepsies, however their relation to the etiology and pharmacological response is unclear. To analyze DTI images in pharmacoresponsive or pharmacoresistant patients with mesial temporal lobe epilepsy (gMTLE and rMTLE, respectively), all with hippocampal sclerosis (HS), frontal lobe epilepsy (FLE) with focal cortical dysplasia (FCD) and normal controls. We enrolled 97 patients (29 with gMTLE, 48 with rMTLE, 20 with FLE-FCD) and 70 controls. MRI was performed on a Phillips 3.0 T scanner. The DTI images were processed using MRICloud.org. We applied Kruskall-Wallis with Dunn-Bonferroni post-hoc comparisons to examine FA and MD values in regions-of-interest (ROI). We set p<0.05 as significant, corrected for false discovery rate. We found a significant reduction in ipsilateral and contralateral FA, and an increase of MD in both groups of patients with MTLE in almost all ROIs compared to controls. Patients with FLE-FCD had less diffuse DTI changes, consisting mainly by bilateral FA reduction in corpus callosum compared to controls (Table 1). WM microstructural are more widespread in patients with MTLE-HS than in FLE-FCD. gMTLE and rMTLE patients presented similar patterns of abnormalities. However, rMTLE patients had WM more intense changes in limbic tracts.

Sex difference in association of symptoms and white matter deficits in first-episode and drug-naive schizophrenia

Accumulating evidence shows that disruption of white matter (WM) may be involved in the pathophysiology of schizophrenia, even at the onset of psychosis. However, very few studies have explored sex difference in its association with psychopathology in schizophrenia. This study aims to compare sex differences in clinical features and WM abnormalities in first-episode and drug-naive (FEDN) schizophrenia among Han Chinese inpatients. The WM fractional anisotropy (FA) values of the whole-brain were determined using voxel-based diffusion tensor imaging (DTI) in 39 (16 males and 23 females) FEDN patients with schizophrenia and 30 healthy controls (13 males and 17 females) matched for gender, age, and education. Patient psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS).Our results showed that compared with the controls, the patients showed widespread areas of lower FA, including corpus callosum, brainstem, internal capsule, cingulate, and cerebellum (all adjusted p < 0.01). Further, male patients showed lower FA values in left cingulate (F = 4.92, p = 0.033), but higher scores on the PANSS total, positive, and general psychopathology subscale scores (all p < 0.01) than female patients. Multivariate regression analysis showed that for male patients, FA values in right corpus callosum were positively associated with the PANSS total (beta = 0.785, t = 3.76, p = 0.002) and the negative symptom scores (beta = 0.494, t = 2.20, p = 0.044), while for female patients, FA values in left cingulate were negatively associated with the PANSS positive symptom score (beta = −0.717, t = −2.25, p = 0.041). Our findings indicate sex difference in white matter disconnectivity and its association with psychopathological symptoms in an early course of schizophrenia onset.

Patients with primary biliary cholangitis and fatigue present with depressive symptoms and selected cognitive deficits, but with normal attention performance and brain structure.

BackgroundIn primary biliary cholangitis (PBC) fatigue is a major clinical challenge of unknown etiology. By demonstrating that fatigue in PBC is associated with an impaired cognitive performance, previous studies have pointed out the possibility of brain abnormalities underlying fatigue in PBC. Whether structural brain changes are present in PBC patients with fatigue, however, is unclear. To evaluate the role of structural brain abnormalities in PBC patients severely affected from fatigue we, therefore, performed a case-control cerebral magnetic resonance imaging (cMRI) study and correlated changes of white and grey brain matter with the cognitive and attention performance.Methods20 female patients with PBC and 20 female age-matched controls were examined in this study. The assessment of fatigue, psychological symptoms, cognitive and attention performance included clinical questionnaires, established cognition tests and a computerized test battery of attention performance. T1-weighted cMRI and diffusion tensor imaging (DTI) scans were acquired with a 3 Tesla scanner. Structural brain alterations were investigated with voxel-based morphometry (VBM) and DTI analyses. Results were correlated to the cognitive and attention performance.ResultsCompared to healthy controls, PBC patients had significantly higher levels of fatigue and associated psychological symptoms. Except for an impairment of verbal fluency, no cognitive or attention deficits were found in the PBC cohort. The VBM and DTI analyses revealed neither major structural brain abnormalities in the PBC cohort nor correlations with the cognitive and attention performance.ConclusionsDespite the high burden of fatigue and selected cognitive deficits, the attention performance of PBC patients appears to be comparable to healthy people. As structural brain alterations do not seem to be present in PBC patients with fatigue, fatigue in PBC must be regarded as purely functional. Future studies should evaluate, whether functional brain changes underlie fatigue in PBC.

Relevance of raised cerebrospinal fluid monocyte levels in patients with frontotemporal dementia

Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder. The contribution of the immune system to its pathogenesis remains incompletely understood. In this study, we performed comprehensive immune cell profiling in the cerebrospinal fluid (CSF) and peripheral blood of patients with FTD. Thirty-two patients with behavioral variant frontotemporal dementia and 25 patients with primary progressive aphasia were included and compared to 14 healthy elderly controls. All patients underwent neuropsychological examination, magnetic resonance imaging, voxel-based diffusion tensor imaging, and peripheral blood and CSF immune cell profiling by multiparameter flow cytometry. The percentage of CSF monocytes was significantly increased specifically in patients with primary progressive aphasia. The proportion of monocytes in the CSF of the total FTD patient group directly correlated with semantic language impairment and microstructural temporal lesions. Increased intrathecal numbers of monocytes suggest a specific response of the innate immune system in a subset of patients with FTD. The findings are of clinical relevance since monocyte levels in the CSF were correlated with typical neuropsychological deficits and microstructural patterns of temporal degeneration.

EPV 4. Contra- and ipsilateral pathway-dependent cortical connectivity mapping of the vestibular network

Introduction Crossing and non-crossing vestibular brainstem fibers provide a rope-ladder system for the bilateral central vestibular network ( Dieterich and Brandt, 2015 ). However, the processing of vestibular information within the human cortex is still poorly understood ( Lopez and Blanke, 2011 ). Aim of this study was to investigate said pathways by means of DTI (diffusion tensor imaging) based on the ipsi- or contralateral pathways found in a recent study using structural and functional connectivity mapping ( Kirsch et al., 2015 ). Methods Twenty-one healthy volunteers (10 females; aged 20–47 years, mean age 27.3 ± 4.9 years) were measured in a 3 Tesla MRI (Erlangen, Siemens, Verio). The data was analyzed with FSL. For the examination of the contra- and ipsilateral pathway-dependent cortical connectivity mapping of the vestibular network we calculated voxelbased DTI tractography between the vestibular nuclei and ipsilateral and contralateral cortical regions using the Juelich histological (cyto- and myelo-architectonic) atlas. Results At group level the data-driven DTI tractography showed distinct contra- and ipsilateral pathway-dependent cortical connectivity mapping of the vestibular network. Interestingly the ipsilateral pathways not only projected to more cortical regions but also the signal intensity was significantly higher in ipsilateral pathways when compared to contralateral pathways regardless of which level of crossing (pons or midbrain). Ipsilateral pathways primarily projected to the operculum 2, posterior insula, BA 1, 2, 3 and 4, superior parietal lobule, lateral geniculate body amygdala and hippocampus. Contralateral pathways projected primarily to the BA 6 and the anterior intraparietal sulcus. Discussion The data confirm a bilateral central vestibular network that is “informed” through a rope-ladder system of crossing and non-crossing vestibular brainstem fibers from both vestibular nuclei. However, the ipsilateral fibres seem to be more crucial and linked to the known multimodal cortical vestibular network ( Guldin et al., 1992 ). This supports results of earlier PET- and fMRI-studies with caloric and galvanic stimulation in humans ( Dieterich and Brandt, 2008 ). The contralateral fibres were fewer and seemed to be primarily linked to perceptual-motor planning and coordination or visual attention.

Effects of Brain Derived Neurotrophic Factor on White Matter Integrity in Middle-Aged Adults: A Voxel-Based Diffusion Tensor Imaging Study (S39.006)

Effects of Brain Derived Neurotrophic Factor on White Matter Integrity in Middle-Aged Adults: A Voxel-Based Diffusion Tensor Imaging Study (S39.006)

Extensive white matter abnormalities and clinical symptoms in drug-naive patients with first-episode schizophrenia: a voxel-based diffusion tensor imaging study.

Increasing evidence shows that disruption of connectivity has been implicated as a central abnormality in schizophrenia, and the alterations in white matter may be the core basis for this disconnection. Diffusion tensor imaging (DTI) has shown white matter abnormalities in first-episode schizophrenia. However, few studies have examined the correlation between clinical symptoms and white matter abnormalities in drug-naive patients with first-episode schizophrenia. The white matter fractional anisotropy (FA) values of the whole-brain were determined by using voxel-based DTI in 39 drug-naive patients with first-episode schizophrenia (diagnosed according to DSM-IV) and 30 healthy controls matched for age and gender. The psychopathology of schizophrenia was assessed with the Positive and Negative Syndrome Scale (PANSS). The study was conducted from April 2009 to March 2010. The patients showed widespread FA reduction in several brain regions, including corpus callosum, brainstem, internal capsule, cingulate, and cerebellum in patients with first-episode schizophrenia when compared to healthy controls (all P values < .01 after adjusting for gender, age, and education). The correlation analysis showed a significant negative correlation between the FA value in the left cerebellum and positive symptoms (r38 = -0.32, P < .05) and a significant positive correlation between the FA values in the corpus callosum and both the PANSS general psychopathology subscore (r38 = 0.39, P < .01) and the PANSS total score (r38 = 0.33, P < .05). Our results indicate that widespread disruption of white matter integrity occurs in an early stage of schizophrenic onset, suggesting an important role in pathogenesis and symptomatology of schizophrenia.

P13. Dendato-thalamo-cortical pathways in association with otolith dysfunction

Introduction The processing of otolith information within the human cortex is still poorly understood (Lopez and Blanke, 2011). Two distinct anatomical otolith pathways within the thalamo-cortical vestibular network were proposed in patients with thalamic infarctions who presented with contra- or ipsiversive tilts of the subjective visual vertical (SVV) (Dieterich and Brandt, 1993; Baier et al., submitted for publication). Aim of this study was to investigate the dendato-thalamo-cortical pathways in association with otolith dysfunction by means of DTI (diffusion tensor imaging) based on the regions found in a recent patient study using statistical lesion-behavior mapping (Baier et al., submitted for publication). Methods Twenty-four healthy volunteers (11 females; aged 20–4years, mean age 28.2±6.3years) were measured in a 3Tesla MRI (Erlangen, Siemens, Verio). The data was analyzed with FSL. For the examination of the dendato-thalamo-cortical pathways we calculated voxelbased DTI tractography between the dendate nuclei, vestibular nuclei, the thalamic regions defined in the patients with thalamic infarctions (Baier et al., submitted for publication) and the cortex. Results At group level the data-driven DTI tractography showed that the dendato-thalamo-cortical pathways connected to ipsiversive SVV tilts projected ipsilaterally from the dendate and vestibular nuclei to the cortex via the caudate nucleus. Thalamus regions connected to contraversive SVV tilts received input from the contralateral cerebellar hemispheres, the dendate and vestibular nucleus crossing either in the pons or mesencephalon and reaching the cortex via the putamen. Discussion These data verify that there are two distinct anatomical otolith signal-processing pathways within a dendato-thalamo-cortical vestibular network. This supports results of earlier PET- and fMRI-studies with caloric and galvanic stimulation in humans (Dieterich and Brandt, 2008). Therefore, our data support the existence of two functionally distinct dendato-thalamo-cortical vestibular pathways leading - when damaged - either to a vestibular tone imbalance to the ipsiversive or to the contraversive side. Acknowledgements Supported by the Support Program for Research and Teaching (FoFoLe LMU ), Graduate School of Systemic Neuroscience (GSN), the German Foundation for Neurology (Deutsche Stiftung Neurologie) and the German Federal Ministry of Education and Research (German Center for Vertigo and Balance Disorders -IFB LMU , Grant code 01 EO 0901).

Regional vulnerability of longitudinal cortical association connectivity: Associated with structural network topology alterations in preterm children with cerebral palsy.

Preterm born children with spastic diplegia type of cerebral palsy and white matter injury or periventricular leukomalacia (PVL), are known to have motor, visual and cognitive impairments. Most diffusion tensor imaging (DTI) studies performed in this group have demonstrated widespread abnormalities using averaged deterministic tractography and voxel-based DTI measurements. Little is known about structural network correlates of white matter topography and reorganization in preterm cerebral palsy, despite the availability of new therapies and the need for brain imaging biomarkers. Here, we combined novel post-processing methodology of probabilistic tractography data in this preterm cohort to improve spatial and regional delineation of longitudinal cortical association tract abnormalities using an along-tract approach, and compared these data to structural DTI cortical network topology analysis. DTI images were acquired on 16 preterm children with cerebral palsy (mean age 5.6 ± 4) and 75 healthy controls (mean age 5.7 ± 3.4). Despite mean tract analysis, Tract-Based Spatial Statistics (TBSS) and voxel-based morphometry (VBM) demonstrating diffusely reduced fractional anisotropy (FA) reduction in all white matter tracts, the along-tract analysis improved the detection of regional tract vulnerability. The along-tract map-structural network topology correlates revealed two associations: (1) reduced regional posterior–anterior gradient in FA of the longitudinal visual cortical association tracts (inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, optic radiation, posterior thalamic radiation) correlated with reduced posterior–anterior gradient of intra-regional (nodal efficiency) metrics with relative sparing of frontal and temporal regions; and (2) reduced regional FA within frontal–thalamic–striatal white matter pathways (anterior limb/anterior thalamic radiation, superior longitudinal fasciculus and cortical spinal tract) correlated with alteration in eigenvector centrality, clustering coefficient (inter-regional) and participation co-efficient (inter-modular) alterations of frontal–striatal and fronto-limbic nodes suggesting re-organization of these pathways. Both along tract and structural topology network measurements correlated strongly with motor and visual clinical outcome scores. This study shows the value of combining along-tract analysis and structural network topology in depicting not only selective parietal occipital regional vulnerability but also reorganization of frontal–striatal and frontal–limbic pathways in preterm children with cerebral palsy. These finding also support the concept that widespread, but selective posterior–anterior neural network connectivity alterations in preterm children with cerebral palsy likely contribute to the pathogenesis of neurosensory and cognitive impairment in this group.

Clinical relevance of specific T-cell activation in the blood and cerebrospinal fluid of patients with mild Alzheimer's disease

In Alzheimer's disease, the contribution of inflammation is still controversially discussed. The aim of this study was to identify a particular immune profile in the peripheral blood (PB) and cerebrospinal fluid (CSF) in patients with mild Alzheimer's disease (mAD) and mild cognitive impairment (MCI) and its potential functional relevance and association with neurodegeneration. A total of 88 patients with cognitive decline (54 mAD, 19 MCI, and 15 other dementias) were included in this study and compared with a group of younger (mean age, 31.3 years) and older (mean age, 68.9 years) healthy volunteers. Patients underwent detailed neurologic and neuropsychological examination, magnetic resonance imaging including voxel-based morphometry of gray matter, voxel-based diffusion tensor imaging, and white matter lesion volumetry, and PB and CSF analysis including multiparameter flow cytometry. Multiparameter flow cytometry revealed that proportions of activated HLA-DR positive CD4+ and CD8+ T-cells were slightly and significantly increased in the PB of MCI and mAD patients, respectively, when compared with healthy elderly controls but not in patients with other dementias. Although only a slight enhancement of the proportion of activated CD4+ T-cells was observed in the CSF of both MCI and mAD patients, the proportion of activated CD8+ T-cells was significantly increased in the CSF of mAD patients when compared with healthy elderly individuals. A slight increase in the proportion of activated CD8+ T-cells was also observed in the intrathecal compartment of MCI patients. Activation of cytotoxic CD8+ T-cells was considerably related to AD-typical neuropsychological deficits. Voxel-based regression analysis revealed a significant correlation between CD8+ T-cell activation and microstructural tissue damage within parahippocampal areas as assessed by diffusion tensor imaging. Taken together, peripheral and intrathecal CD8+ T-cell activation in mAD was significantly different from other dementias, suggesting a specific adaptive immune response. Lymphocyte activation seems to have a clinical impact because levels of activated CD8+ T-cells were correlated with clinical and structural markers of AD pathology.

Aphasia Severity in Chronic Stroke Patients

Background. The contribution of lesion size and location in poststroke aphasia is debated, especially the extent to which aphasia severity is affected by damage to specific white matter areas. Objective. To identify specific white matter areas critical for poststroke aphasia global severity and to determine whether injury to these areas had more impact on aphasia severity than the infarct volume. Methods. Twenty-three chronic poststroke aphasic patients were assessed with the Aphasia Rapid Test (ART) and the Boston Diagnosis Aphasia Examination (BDAE) global severity scales and underwent diffusion tensor and structural imaging. Voxel-based diffusion tensor imaging regression analysis was used to determine in which areas fractional anisotropy (FA) abnormalities were correlated with ART and BDAE severity scales. The relationships between aphasia severity, FA values, and infarct volumes were investigated using global and partial correlations. Results. We found a critical area associated with aphasia severity overlapping with the arcuate and the inferior fronto-occipital fasciculi, resulting in a combined disconnection of the dorsal and ventral pathways. ART scores were inversely correlated with FA values in this region, with greater severity present with lower FA values (correlation coefficient = −0.833, P < .0001). The proportion of variance explained by the FA value was higher than the proportion of variance explained by the infarct volume (R2 = 68% vs 27%, P = .01). The impact of infarct volume on aphasia severity disappeared when damage to this critical white matter area was taken into account (P = .38). Conclusion. The assessment of the integrity of this region may potentially have a clinical impact in neurorehabilitation and acute decision making.

Characterization of microstructural injury: a novel approach in infant abusive head trauma-initial experience.

Abusive head trauma (AHT) is the leading cause of morbidity and mortality among abused children, yet the neuroanatomical underpinnings of AHT outcome is incompletely understood. The aim of this study was to characterize white matter (WM) abnormalities in infants with AHT using diffusion tensor imaging (DTI) and determine which microstructural abnormalities are associated with poor outcome. Retrospective DTI data from 17 infants (>3 months) with a diagnosis of AHT and a comparison cohort of 34 term infants of similar post-conceptual age (PCA) were compared using a voxel-based DTI analysis of cerebral WM. AHT cases were dichotomously classified into mild/moderate versus severe outcome. Clinical variables and conventional imaging findings were also analyzed in relation to outcome. Outcomes were classified in accordance with the Pediatric Cerebral Performance Category Score (PCPCS). Reduced axial diffusivity (AD) was shown in widespread WM regions in the AHT infants compared with controls as well as in the AHT severe outcome group compared with the AHT mild/moderate outcome group. Reduced mean diffusivity (MD) was also associated with severe outcome. Radial diffusivity (RD), conventional magnetic resonance findings, brain metric measurements, and clinical/laboratory variables (with the exception of Glascow Coma Scale) did not differ among AHT outcome groups. Findings support the unique role of DTI techniques, beyond conventional imaging, in the evaluation of microstructural WM injury of AHT. Reduced AD (likely reflecting axonal damage) and MD were associated with poor clinical outcome. DTI abnormalities may uniquely reflect AHT patterns of axonal injury that are not characterized by conventional imaging, which may have both therapeutic and prognostic implications.

Diffusion tensor imaging study of white matter damage in chronic meningitis.

Tuberculous meningitis (TBM) and cryptococcal meningitis (CM) are two of the most common types of chronic meningitis. This study aimed to assess whether chronic neuro-psychological sequelae are associated with micro-structure white matter (WM) damage in HIV-negative chronic meningitis. Nineteen HIV-negative TBM patients, 13 HIV-negative CM patients, and 32 sex- and age-matched healthy volunteers were evaluated and compared. The clinical relevance of WM integrity was studied using voxel-based diffusion tensor imaging (DTI) magnetic resonance imaging. All of the participants underwent complete medical and neurologic examinations, and neuro-psychological testing. Differences in DTI indices correlated with the presence of neuro-psychological rating scores and cerebrospinal fluid (CSF) analysis during the initial hospitalization. Patients with CM had more severe cognitive deficits than healthy subjects, especially in TBM. There were changes in WM integrity in several limbic regions, including the para-hippocampal gyrus and cingulate gyrus, and in the WM close to the globus pallidus. A decline in WM integrity close to the globus pallidus and anterior cingulate gyrus was associated with worse CSF analysis profiles. Poorer DTI parameters directly correlated with worse cognitive performance on follow-up. These correlations suggest that WM alterations may be involved in the psychopathology and pathophysiology of co-morbidities. Abnormalities in the limbic system and globus pallidus, with their close relationship to the CSF space, may be specific biomarkers for disease evaluation.