Fractional Anisotropy Reduction Research Articles

Characterization of white matter changes along fibers by automated fiber quantification in the early stages of Alzheimer's disease.

Brain white matter fiber bundles in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) have abnormalities not usually seen in unaffected subjects. Ideal algorithm of the localization-specific properties in white matter integrity might reveal the changes of tissue properties varying along each tract, while previous studies only detected the mean DTI parameters of each fiber. The aim of this study was to investigate whether these abnormalities of nerve fiber tracts are localized to specific regions of the tracts or spread throughout and to analyze which of the examined fiber tracts are involved in the early stages of Alzheimer's disease. In this study, we utilized VBA, TBSS as well as AFQ together to comprehensively investigate the white matter fiber impairment on 25 CE patients, 29 MCI patients and 34 normal control (NC) subjects. Two tract profiles, fractional anisotropy (FA) and mean diffusivity (MD), were extracted to evaluate the white matter integrity at 100 locations along each of 20 fiber tracts and then we validated the results with 27 CE patients, 21 MCI patients and 22 NC from the ADNI cohort. Also, we compare the AFQ with VBA and TBSS in our cohort. In comparison with NC, AD patients showed widespread FA reduction in 25% (5 /20) and MD increase in 65%(13/20) of the examined fiber tracts. The MCI patients showed a regional FA reduction in 5% (1/20) of the examined fiber tracts (right cingulum cingulate) and MD increase in 5%(1/20) of the examined fiber tracts (left arcuate fasciculus). Among these changed tracts, only the right cingulum cingulate showed widespread disruption of myelin or/and fiber axons in MCI and aggravated deterioration in AD, findings supported by FA/MD changes both by the mean and FA changes by point wise methods and TBSS. And the AFQ findings from ADNI cohort showed some similarity with our cohort, especially in the pointwise comparison of MD profiles between AD vs NC. Furthermore, the pattern of white matter abnormalities was different across neuronal fiber tracts; for example, the MCI and AD patients showed similar FA reduction in the middle part of the right cingulum cingulate, and the anterior part were not damaged. However, the left arcuate fasciculus showed MD elevation located at the temporal part of the fibers in the MCI patients and expanding to the temporal and middle part of the fibers in AD patients. So, the AFQ may be an alternative complementary method of VBA and TBSS, and may provide new insights into white matter degeneration in MCI and its association with AD.

Psychoradiologic abnormalities of white matter in patients with bipolar disorder: diffusion tensor imaging studies using tract-based spatial statistics

An increasing number of psychoradiology studies that use tract-based spatial statistics (TBSS) of diffusion tensor imaging have reported abnormalities of white matter in patients with bipolar disorder; however, robust conclusions have proven elusive, especially considering some important clinical and demographic factors. In the present study, we performed a quantitative meta-analysis of TBSS studies to elucidate the most consistent white-matter abnormalities in patients with bipolar disorder. We conducted a systematic search up to May 2017 for all TBSS studies comparing fractional anisotropy (FA) between patients with bipolar disorder and healthy controls. We performed anisotropic effect size–signed differential mapping meta-analysis. We identified a total of 22 data sets including 556 patients with bipolar disorder and 623 healthy controls. We found significant FA reductions in the genu and body of the corpus callosum in patients with bipolar disorder relative to healthy controls. No regions of increased FA were reported. In subgroup analyses, the FA reduction in the genu of the corpus callosum retained significance in patients with bipolar disorder type I, and the FA reduction in the body of the corpus callosum retained significance in euthymic patients with bipolar disorder. Meta-regression analysis revealed that the percentage of female patients was negatively correlated with reduced FA in the body of the corpus callosum. Data acquisition, patient characteristics and clinical variables in the included studies were heterogeneous. The small number of diffusion tensor imaging studies using TBSS in patients with bipolar disorder type II, as well as the lack of other clinical information, hindered the application of subgroup meta-analyses. Our study consistently identified decreased FA in the genu and body of the corpus callosum, suggesting that interhemispheric communication may be the connectivity most affected in patients with bipolar disorder.

The same cortico-efferent tract involvement in progressive bulbar palsy and in 'classical' ALS: A tract of interest-based MRI study.

BackgroundThere is an ongoing debate about the concept of restricted phenotypes of amyotrophic lateral sclerosis (ALS), including progressive bulbar palsy (PBP).ObjectiveThe study was designed to investigate specific white matter alterations in diffusion tensor imaging (DTI) data from PBP patients using a hypothesis-guided tract-of-interest-based approach (compared with ‘classical’ ALS patients and controls) to identify in vivo microstructural changes according to the neuropathologically defined ALS-related corticoefferent tract pathology.MethodsDTI-based white matter mapping was performed both by an unbiased voxel-wise statistical comparison and by a hypothesis-guided tract-wise analysis of fractional anisotropy (FA) maps according to the ALS-staging pattern for 23 PBP and 23 ALS patients vs 23 matched controls.ResultsThe analysis of white matter integrity demonstrated regional FA reductions along the CST and also in frontal and prefrontal brain areas both in PBP patients and ALS patients with additional regional FA reduction in the pons of the PBP group. In the tract-specific analysis according to the neuropathological ALS-staging pattern, PBP and ALS patients showed identical significant alterations of ALS-related tract systems when compared with controls.ConclusionsThe DTI study including the tract-of-interest-based analysis showed the same microstructural corticoefferent involvement patterns in PBP patients as in ALS, which supports the hypothesis that PBP is a phenotypical variant of ALS.

Altered volume and microstructural integrity of hippocampus in NMOSD

ObjectiveTo assess whole and subfield volume and microstructural integrity of the hippocampus in patients with neuromyelitis optical spectrum disorder (NMOSD), and whether these alterations are correlated with expanded disability status scale (EDSS), anxiety score and depression score. MethodsThe volume of the hippocampus and twelve hippocampal subfields, together with fractional anisotropy (FA) and mean diffusivity (MD) were measured in thirty patients with NMOSD and twenty-six healthy controls. EDSS score, anxiety score and depression score were measured in all participants. The relationships between whole hippocampal volume, subfield volume, hippocampal microstructural integrity and clinical and behavioral test scores were investigated. ResultsSignificantly decreased total volume, decreased FA and increased MD were observed in the hippocampus bilaterally in NMOSD. The reductions in left presubiculum, subiculum, CA1, CA4, GC-DG, molecular layer and right presubiculum (p < .004) remained significant after Bonferroni correction. Hippocampal volume reductions, FA reductions and MD increases were correlated with anxiety and depression scores. ConclusionsThis study reveals that patients with NMOSD have decreased volume and altered microstructural integrity of the hippocampus. Furthermore, certain of these alterations are correlated with severity of anxiety and depression. Further investigation of these findings may provide insight to improve clinical management and treatment of NMOSD patients with mood disorders.

Functional and Structural Brain Plasticity in Adult Onset Single-Sided Deafness.

Single-sided deafness (SSD) or profound unilateral hearing loss obligates the only serviceable ear to capture all acoustic information. This loss of binaural function taxes cognitive resources for accurate listening performance, especially under adverse environments or challenging tasks. We hypothesized that adults with SSD would manifest both functional and structural brain plasticity compared to controls with normal binaural hearing. We evaluated functional alterations using magnetoencephalographic imaging (MEGI) of brain activation during performance of a moderately difficult auditory syllable sequence reproduction task and assessed structural integrity using diffusion tensor imaging (DTI). MEGI showed the SSD cohort to have increased induced oscillations in the theta band over the left superior temporal cortex and decreased induced gamma band oscillations over the frontal and parietal cortices between 175 and 475 ms following stimulus onset. DTI showed the SSD cohort to have extensive fractional anisotropy (FA) reduction in both auditory and non-auditory tracts and regions. Overlaying functional and structural changes revealed by the two imaging techniques demonstrated close registration of cortical areas and white matter tracts that expressed brain plasticity. Hence, complete loss of input from one ear in adulthood triggers both functional and structural alterations to dorsal temporal and frontal-parietal areas.

FDG-PET hypometabolism is more sensitive than MRI atrophy in Parkinson's disease: A whole-brain multimodal imaging meta-analysis.

Recently, revised diagnostic criteria for Parkinson's disease (PD) were introduced (Postuma et al., 2015). Yet, except for well-established dopaminergic imaging, validated imaging biomarkers for PD are still missing, though they could improve diagnostic accuracy.We conducted systematic meta-analyses to identify PD-specific markers in whole-brain structural magnetic resonance imaging (MRI), [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) and diffusion tensor imaging (DTI) studies. Overall, 74 studies were identified including 2323 patients and 1767 healthy controls. Studies were first grouped according to imaging modalities (MRI 50; PET 14; DTI 10) and then into subcohorts based on clinical phenotypes. To ensure reliable results, we combined established meta-analytical algorithms - anatomical likelihood estimation and seed-based D mapping - and cross-validated them in a conjunction analysis.Glucose hypometabolism was found using FDG-PET extensively in bilateral inferior parietal cortex and left caudate nucleus with both meta-analytic methods. This hypometabolism pattern was confirmed in subcohort analyses and related to cognitive deficits (inferior parietal cortex) and motor symptoms (caudate nucleus). Structural MRI showed only small focal gray matter atrophy in the middle occipital gyrus that was not confirmed in subcohort analyses. DTI revealed fractional anisotropy reductions in the cingulate bundle near the orbital and anterior cingulate gyri in PD.Our results suggest that FDG-PET reliably identifies consistent functional brain abnormalities in PD, whereas structural MRI and DTI show only focal alterations and rather inconsistent results. In conclusion, FDG-PET hypometabolism outperforms structural MRI in PD, although both imaging methods do not offer disease-specific imaging biomarkers for PD.

Sequential phases of RGC axonal and somatic injury in EAE mice examined using DTI and OCT

BackgroundClinical imaging modalities including optical coherence tomography (OCT) and diffusion tensor imaging (DTI) are vital in Multiple Sclerosis (MS), but their relationships during the different phases of Retinal ganglion cell (RGC) degeneration are not clear. We hypothesize that initial injury in optic nerve causes axonal degeneration leading to RGC loss in retina, which can be characterized by a combination of DTI and OCT. Our objective was to examine the correlation between noninvasive and histological data to chronicle the degeneration profile of RGCs in the retina and optic nerve in a mouse model of MS. Materials and methodsExperimental Autoimmune Encephalomyelitis (EAE) was induced in 11 C57Bl/6 mice, with 8 mice reserved as controls. OCT and DTI was conducted 2–8 weeks after induction of EAE. The thickness of the retinal ganglion cell complex (GCC) was measured using OCT and compared to DTI indices measured in optic nerves. End-stage histology was used to quantify axon/myelin loss in the optic nerve and retinal thinning/RGC loss in the retina. ResultsSignificant changes in DTI-derived Axial Diffusivity (AD, −17.2%) and Trace Diffusivity (TR, −18.3%) began after 2 weeks of EAE. Later significant reductions in Fractional Anisotropy (FA) and AD, with increases in Radial Diffusion (RD) were apparent after 4 and 8 weeks. OCT-derived measures of GCC thickness were reduced after 4 weeks, and reached significant reduction after 8 weeks. Among EAE mice, DTI (FA, AD and RD measures) and OCT measures were all significantly correlated after 4 and 8 weeks. Among histology measures, RGC density (−23%), RGC size (−27%), and the number of SMI31+ axons (−54%) were reduced significantly. DTI measures of FA and AD along with GCC thinning were the best independent predictors of axon loss. ConclusionsDTI and OCT measures are tightly correlated during the chronic phase of axonal degeneration (4–8 weeks) in EAE mice. After 8 weeks of EAE, both OCT and DTI measures are strong predictors of axon loss in the Optic Nerve.

Antipsychotics and Their Impact on Cerebral White Matter: Part of the Problem or Part of the Solution?

Antipsychotics and Their Impact on Cerebral White Matter: Part of the Problem or Part of the Solution?

Optimal parameters and location for diffusion tensor imaging in the diagnosis of carpal tunnel syndrome: a meta-analysis

To assess the diagnostic value of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of diffusion tensor imaging (DTI) at several anatomical locations in patients with carpal tunnel syndrome (CTS) to explore the optimal parameters and measurement location. A search was conducted using the PubMed, EBSCO, Ovid, Web of Science, and Cochrane databases to identify articles relevant to this study published before September 2017. Studies were selected and included according to strict eligibility criteria. Mean differences (MD) and 95% confidence intervals (CIs) were used to compare FA and ADC values between CTS patients and healthy subjects. Potential publication bias was investigated. Eleven studies involving 349 CTS wrists and 278 controls were selected for the meta-analysis. A notable MD: was found for lowered FA at the level of the pisiform bone for CTS versus controls (MD: -0.11, 95% confidence interval [CI]: -1.14 to -0.07, z=5.83, p<0.001). A higher ADC was found at the pisiform bone and hamate bone levels for CTS versus controls (P: MD: 0.15, 95% CI: 0.10 to 0.20, z=5.98, p<0.001, H: MD: 0.15; 95% CI: 0.09 to 0.21, z=4.67, p<0.001). The meta-analysis demonstrated a significant FA reduction and ADC increase in CTS patients. This result supports the use of DTI parameters in differentiating CTS patients from health subjects. The anatomical site for FA at the pisiform and ADC at the pisiform and hamate levels were more accessible than other sites for the diagnosis of CTS patients.

White matter aberrations and age-related trajectories in patients with schizophrenia and bipolar disorder revealed by diffusion tensor imaging

Supported by histological and genetic evidence implicating myelin, neuroinflammation and oligodendrocyte dysfunction in schizophrenia spectrum disorders (SZ), diffusion tensor imaging (DTI) studies have consistently shown white matter (WM) abnormalities when compared to healthy controls (HC). The diagnostic specificity remains unclear, with bipolar disorders (BD) frequently conceptualized as a less severe clinical manifestation along a psychotic spectrum. Further, the age-related dynamics and possible sex differences of WM abnormalities in SZ and BD are currently understudied. Using tract-based spatial statistics (TBSS) we compared DTI-based microstructural indices between SZ (n = 128), BD (n = 61), and HC (n = 293). We tested for age-by-group and sex-by-group interactions, computed effect sizes within different age-bins and within genders. TBSS revealed global reductions in fractional anisotropy (FA) and increases in radial (RD) diffusivity in SZ compared to HC, with strongest effects in the body and splenium of the corpus callosum, and lower FA in SZ compared to BD in right inferior longitudinal fasciculus and right inferior fronto-occipital fasciculus, and no significant differences between BD and HC. The results were not strongly dependent on age or sex. Despite lack of significant group-by-age interactions, a sliding-window approach supported widespread WM involvement in SZ with most profound differences in FA from the late 20 s.

Cerebrospinal fluid biomarkers predict frontotemporal dementia trajectory.

ObjectiveThe prognostic value of cerebrospinal fluid neurofilament light chain, total tau, phosphorylated tau181, and amyloid beta1‐42 was examined in frontotemporal dementia subtypes.MethodsWe compared baseline biomarkers between 49 controls, 40 patients with behavioral variant frontotemporal dementia, 24 with semantic variant primary progressive aphasia, and 26 with nonfluent variant primary progressive aphasia. Linear mixed effect models were used to assess the value of baseline biomarkers in predicting clinical and radiographic change in patient cohorts over multiple yearly follow up visits.ResultsNeurofilament light chain concentrations were lowest in controls. Elevated baseline neurofilament light chain predicted faster worsening in clinical severity, frontotemporal volume and frontotemporal fractional anisotropy in patients with behavioral variant frontotemporal dementia and nonfluent variant primary progressive aphasia. High total tau similarly predicted faster progression in nonfluent variant primary progressive aphasia. In behavioral variant frontotemporal dementia, higher phosphorylated tau181 predicted faster clinical progression whereas lower amyloid beta1‐42 predicted faster volumetric and fractional anisotropy reduction. Neurofilament light chain and phosphorylated tau181 were of greater predictive value in patients with tau pathology as compared to TDP‐43 pathology. Baseline neurofilament light chain correlated with baseline clinical severity and frontotemporal volume in behavioral variant frontotemporal dementia. Baseline total tau correlated with baseline clinical severity in semantic variant primary progressive aphasia.InterpretationHigh cerebrospinal fluid neurofilament light chain predicts more aggressive disease in behavioral variant frontotemporal dementia and nonfluent variant primary progressive aphasia. Total tau, phosphorylated tau181, and amyloid beta1‐42 also predict some measures of disease aggressiveness in frontotemporal dementia.

281 Predicting neurodegeneration after traumatic brain injury

BackgroundDementia rates are elevated after traumatic brain injury (TBI) and a subgroup develops chronic traumatic encephalopathy. Post-traumatic neurodegeneration can be measured by brain atrophy rates derived from neuroimaging, but it is unclear how atrophy relates to the initial pattern of injury.ObjectivesTo investigate the relationship between baseline TBI patterns and subsequent neurodegeneration measured by progressive brain atrophy.Methods55 patients after moderate-severe TBI (mean 3 years post-injury) and 20 controls underwent longitudinal MRI. Brain atrophy was quantified using the Jacobian determinant defined from volumetric T1 scans approximately one year apart. Diffuse axonal injury was measured using diffusion tensor imaging and focal injuries defined from T1 and FLAIR. Neuropsychological assessment was performed.ResultsAbnormal progressive brain atrophy was seen after TBI (~1.8%/year in white matter). This was accompanied by widespread reductions in fractional anisotropy, in keeping with the presence of diffuse axonal injury. There was a strong negative correlation between FA and brain atrophy, whereby areas of greater white matter damage showed greater atrophy over time.ConclusionsThe results show a strong relationship between the location of diffuse axonal injury and subsequent neurodegeneration. This suggests that TBI triggers progressive neurodegeneration through the long-lasting effects of diffuse axonal injury.

Functional and Structural Brain Damage in Friedreich's Ataxia.

Friedreich's ataxia (FRDA) is a rare hereditary neurodegenerative disorder caused by a GAA repeat expansion in the FXN gene. There is still no cure or quantitative biomarkers reliaby correlating with the progression rate and disease severity. Investigation of functional and structural alterations characterizing white (WM) and gray matter (GM) in FRDA are needed prerequisite to monitor progression and response to treatment. Here we report the results of a multimodal cross-sectional MRI study of FRDA including Voxel-Based Morphometry (VBM), diffusion-tensor imaging (DTI), functional MRI (fMRI), and a correlation analysis with clinical severity scores. Twenty-one early-onset FRDA patients and 18 age-matched healthy controls (HCs) were imaged at 3T. All patients underwent a complete cognitive and clinical assessment with ataxia scales. VBM analysis showed GM volume reduction in FRDA compared to HCs bilaterally in lobules V, VI, VIII (L>R), as well as in the crus of cerebellum, posterior lobe of the vermis, in the flocculi and in the left tonsil. Voxel-wise DTI analysis showed a diffuse fractional anisotropy reduction and mean, radial, axial (AD) diffusivity increase in both infratentorial and supratentorial WM. ROI-based analysis confirmed the results showing differences of the same DTI metrics in cortico-spinal-tracts, forceps major, corpus callosum, posterior thalamic radiations, cerebellar penduncles. Additionally, we observed increased AD in superior (SCP) and middle cerebellar peduncles. The WM findings correlated with age at onset (AAO), short-allelle GAA, and disease severity. The intragroup analysis of fMRI data from right-handed 14 FRDA and 15 HCs showed similar findings in both groups, including activation in M1, insula and superior cerebellar hemisphere (lobules V–VIII). Significant differences emerged only during the non-dominant hand movement, with HCs showing a stronger activation in the left superior cerebellar hemisphere compared to FRDA. Significant correlations were found between AAO and the fMRI activation in cerebellar anterior and posterior lobes, insula and temporal lobe. Our multimodal neuroimaging protocol suggests that MRI is a useful tool to document the extension of the neurological impairment in FRDA.

White Matter Abnormalities in Never-Treated Patients With Long-Term Schizophrenia.

This study tested for differences of white matter integrity between treated and never-treated long-term schizophrenia patients, matched on illness duration, and for differential changes in relation to age in these two groups relative to healthy comparison subjects. This cross-sectional diffusion tensor imaging study included 31 never-treated and 46 matched antipsychotic-treated patients with long-term schizophrenia and 58 healthy comparison subjects. Fractional anisotropy measures of white matter tracts were extracted and compared. Linear regression analysis was used to explore the association between age and fractional anisotropy among the three groups. Fractional anisotropy significantly differed among the three groups in 14 of 20 white matter tracts defined in the Johns Hopkins University white matter template. Never-treated patients displayed greater reduction of fractional anisotropy than antipsychotic-treated patients in the left anterior thalamic radiation, the left cingulum-hippocampus pathway, the splenium and genu of the corpus callosum, and the left superior longitudinal fasciculus, and greater fractional anisotropy in the right uncinate fasciculus. Both patient groups showed multiple reductions relative to healthy comparison subjects. Never-treated patients showed an accelerated and clinically relevant age-related reduction of fractional anisotropy in the genu of the corpus callosum. These psychoradiological findings provide insight into the regional distribution of white matter deficits in the years after illness onset in long-term schizophrenia. Findings of greater impairments in never-treated patients, and a greater age-related reduction in the genu of the corpus callosum in these patients, suggest that long-term antipsychotic treatment does not adversely affect white matter tracts over the longer-term course of illness and may confer benefits.

A Follow-up Study of Postoperative DCM Patients Using Diffusion MRI with DTI and NODDI.

A retrospective cohort study. The aim of this study was to investigate the relationship between spinal cord microstructures and spinal cord dysfunction in degenerative cervical myelopathy (DCM) patients; a follow-up study was carried out using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), an advanced diffusion model. DTI has been used for diagnosis of DCM. Although DTI has advantages of high sensitivity and quantitative features, it is limited by its low specificity for measuring microstructures. Fifty-eight postoperative DCM patients with 12 to 14 months of surgical recovery were recruited, as well as 14 healthy volunteers for control group. All DTI and NODDI metrics were measured at the most stenotic levels of patients and at all levels of control group. A t test was used to compare the metrics between patient and control groups, and Spearman correlation was used to test the relationship between the metrics and clinical assessment, modified Japanese Orthopedic Association (mJOA) scores. t test showed that DTI metrics, neurite density Vic, and free water fraction Viso had significant differences between control group and the most stenotic levels in patients. For DTI metrics, fractional anisotropy (FA), radial diffusivity (RD), and mean diffusivity (MD) in patients were significantly correlated with mJOA. For NODDI metrics, only Vic is positively correlated with mJOA. The results of t test and correlation with mJOA suggest that DTI and NODDI are valuable for evaluating spinal cord function. Results of NODDI indicate that the reason for FA reduction in DCM may be decreased neurite density, not increased orientation dispersion. 3.

Evaluation of neuregulin-1's neuroprotection against ischemic injury in rats using diffusion tensor imaging

Stroke is a devastating neurovascular disorder that results in damage to neurons and white matter tracts. It has been previously demonstrated that neuregulin-1 (NRG-1) protects neurons from ischemic injury following stroke. Here, diffusion tensor imaging (DTI) was utilized to characterize the effects of NRG-1 treatment on cererbral infarction and integrity of white matter after ischemic insult using a permanent middle celebral artery occlusion (pMCAo) rat model. In the present study, sixteen Sprague-Dawley rats underwent pMCAo surgery and received either a single intra-arterial bolus (20 μg/kg) dose of NRG-1 or saline immediately prior to pMCAo. MRI including T2-weighted imaging and DTI was performed in the first 3 h post stroke, and repeated 48 h later. It is found that the stroke infarction was significantly reduced in the NRG-1 treated group. Also, NRG-1 prevented the reduction of fractional anisotropy (FA) in white matter tracts of fornix and corpus callosum (CC), indicating its protection of CC and fornix white matter bundles from ischemia insult. As a conclusion, the present DTI results demonstrate that NRG-1 has significantly neuroprotective effects in both cerebral cortex and white matter including corpus callosum and fornix during acute stroke. In particular, NRG-1 is more effective on stroke lesion with mild ischemia. As CC and fornix white matter bundles play critical roles in transcallosal connectivity and hippocampal projections respectively in the central nervous system, the findings could provide complementary information for better understanding the biological mechanism of NRG-1's neuroprotection in ischemic tissues and neurobehavioral effects.

FV7. Tract of interest-based DTI analysis in upper and lower motor neuron disease variants of ALS

Background It is still a topic of research if specific clinical presentations of motoneuron disease (MND) patients should be classified as amyotrophic lateral sclerosis (ALS) variants, i.e. primary lateral sclerosis (PLS) with predominant upper motor neuron on the one hand and pure lower motor neuron disease (LMND) on the other hand. Objective markers for ALS are to be investigated in these patients. Objective The aim of the study was to investigate white matter damage by a hypothesis-guided tract-of-interest-based approach in patients with classical ALS, LMND, and PLS in contrast to healthy controls in order to challenge the hypothesis that brain structural changes according to the neuropathologically defined ALS affectation pattern ( Kassubek et al., 2014 ) can be observed. LMND data were pooled from previous studies at two different study sites (Ulm, Germany and Milano, Italy). Methods DTI-based white matter integrity mapping was performed by voxelwise statistical comparison and by a tractwise analysis of fractional anisotropy (FA) maps according to the ALS-staging pattern for 65 LMND patients (clinically differentiated in fast and slow progressors), 42 PLS patients, and 101 ALS patients with a ’classical’ phenotype vs 92 matched controls to identify white matter structural alterations. Results The analysis of predefined tracts-of-interest according to the neuropathological spreading pattern demonstrated regional characteristic alteration patterns (FA reductions) fast LMND progressors and in ALS compared to controls. ( Muller et al., 2018 ) The degree of involvement correlated with the clinical phenotype. PLS also presented substantial tract involvement in the tract-of-interest-based approach. Conclusion In the tract-specific analysis according to the ALS-staging pattern, upper (PLS) as well as lower motor neuron disease (LMND) pathology showed alterations of ALS-related corticoefferent fibers. The neuroimaging results confirm the clinical approach to these phenotypes as ALS variants, in accordance with the latest revision of the El Escorial criteria for ALS, in favour of the consequence to treat these patients like ALS and also to include them into clinical trials of ALS.

What Can Be Learned from Diffusion Tensor Imaging from a Large Traumatic Brain Injury Cohort?: White Matter Integrity and Its Relationship with Outcome.

Traumatic axonal injury (TAI) contributes significantly to mortality and morbidity after traumatic brain injury (TBI), but its identification is still a diagnostic challenge because of the limitations of conventional imaging techniques to characterized it. Diffusion tensor imaging (DTI) can indirectly identify areas of damaged white matter (WM) integrity by detecting water molecule diffusion alterations. Therefore, DTI may improve detection and description of TAI lesions after TBI. We have obtained DTI data from 217 patients with moderate to severe TBI acquired at a median of 19 days after TBI, and patient DTI metrics were compared with data obtained from 58 age-matched healthy controls. Region of interest (ROI) method was applied to obtain mean fractional anisotropy (FA) value in 28 WM fiber bundles susceptible to TAI. Our main results were that when we compared patients with controls, patients, regardless of TBI severity, showed significantly reduced mean FA in almost all ROI measured. We found statistically significant correlation between FA metrics and some demographic, clinical, and conventional imaging characteristics. Additionally, these FA metrics were highly associated with outcome assessed at hospital discharge and at 6 and 12 months after TBI. We conclude that FA reduction in the subacute stage after TBI assessed by DTI may be a useful prognostic factor for long-term unfavorable outcome.

White matter connectivity between occipital and temporal regions involved in face and voice processing in hearing and early deaf individuals

Neuroplasticity following sensory deprivation has long inspired neuroscience research in the quest of understanding how sensory experience and genetics interact in developing the brain functional and structural architecture. Many studies have shown that sensory deprivation can lead to cross-modal functional recruitment of sensory deprived cortices. Little is known however about how structural reorganization may support these functional changes. In this study, we examined early deaf, hearing signer and hearing non-signer individuals using diffusion MRI to evaluate the potential structural connectivity linked to the functional recruitment of the temporal voice area by face stimuli in deaf individuals. More specifically, we characterized the structural connectivity between occipital, fusiform and temporal regions typically supporting voice- and face-selective processing. Despite the extensive functional reorganization for face processing in the temporal cortex of the deaf, macroscopic properties of these connections did not differ across groups. However, both occipito- and fusiform-temporal connections showed significant microstructural changes between groups (fractional anisotropy reduction, radial diffusivity increase). We propose that the reorganization of temporal regions after early auditory deprivation builds on intrinsic and mainly preserved anatomical connectivity between functionally specific temporal and occipital regions.

Abnormalities in thalamo-cortical connections in patients with first-episode schizophrenia: a two-tensor tractography study.

The "cognitive dysmetria" hypothesis suggests that impairments in cognition and behavior in patients with schizophrenia can be explained by disruptions in the cortico-cerebellar-thalamic-cortical circuit. In this study we examine thalamo-cortical connections in patients with first-episode schizophrenia (FESZ). White matter pathways are investigated that connect the thalamus with three frontal cortex regions including the anterior cingulate cortex (ACC), ventrolateral prefrontal cortex (VLPFC), and lateral oribitofrontal cortex (LOFC). We use a novel method of two-tensor tractography in 26 patients with FESZ compared to 31 healthy controls (HC), who did not differ on age, sex, or education. Dependent measures were fractional anisotropy (FA), Axial Diffusivity (AD), and Radial Diffusivity (RD). Subjects were also assessed using clinical functioning measures including the Global Assessment of Functioning (GAF) Scale, the Global Social Functioning Scale (GF: Social), and the Global Role Functioning Scale (GF: Role). FESZ patients showed decreased FA in the right thalamus-right ACC and right-thalamus-right LOFC pathways compared to healthy controls (HCs). In the right thalamus-right VLPFC tract, we found decreased FA and increased RD in the FESZ group compared to HCs. After correcting for multiple comparisons, reductions in FA in the right thalamus- right ACC and the right thalamus- right VLPC tracts remained significant. Moreover, reductions in FA were significantly associated with lower global functioning scores as well as lower social and role functioning scores. We report the first diffusion tensor imaging study of white matter pathways connecting the thalamus to three frontal regions. Findings of white matter alterations and clinical associations in the thalamic-cortical component of the cortico-cerebellar-thalamic-cortical circuit in patients with FESZ support the cognitive dysmetria hypothesis and further suggest the possible involvement of myelin sheath pathology and axonal membrane disruption in the pathogenesis of the disorder.