Age‐related microstructural changes in subcortical white matter during postadolescent periods in men revealed by diffusion‐weighted MR imaging

Continuous maturation of cerebral white matter (WM) in the postadolescent period is not fully understood. To elucidate the time course and location of possible postadolescent maturational changes in cerebral WM, we studied 60 healthy male subjects who were in their second to seventh decade using diffusion‐weighted imaging. Mean diffusivity (MD) in subcortical WM was measured in 78 cortical regions in each subject's brain using an automated method. Regression analysis was used to model the age‐related change in MD by either a linear or a quadratic function in each region. Age‐related changes in subcortical MD were best modeled by either a linear function or a quadratic function in 27 regions including language‐related regions, visual or multimodal areas in the bilateral occipital and temporal lobes, limbic areas including the bilateral parahippocampal gyri, and the bilateral postcentral and left precentral gyri. In these regions, the MD rapidly decreased until middle age and thereafter reached a plateau. Our results revealed microstructural changes in local subcortical WM and suggests a continuing maturational process in postoadolescent periods. Hum Brain Mapp 2009. © 2009 Wiley‐Liss, Inc.     

Difference of the hippocampal and white matter microalterations in MCI patients according to the severity of subcortical vascular changes: neuropsychological correlates of diffusion tensor imaging

OBJECTIVES: Most imaging studies of mild cognitive impairment (MCI) have focused on gray matter alterations, although many MCI patients demonstrate subcortical vascular changes. We investigated the changes of the hippocampal area and various white matter areas in MCI patients with using diffusion tensor imaging (DTI), according to the severity of subcortical vascular changes, and we then correlated the DTI findings with the neuropsychological results. PATIENTS AND METHODS: Among the 40 MCI patients, the 21 non-vascular MCI (nvMCI) and 19 vascular MCI (vMCI) patients were subdivided according to Erkinjuntti's imaging criteria. The mean diffusivity (MD) and fractional anisotropy (FA) were compared in the bilateral temporal, frontal, parietal and occipital white matter regions, as well as in the bilateral hippocampi, centrum semiovale, and the midline genu and splenum of the corpus callosum among the nvMCI and vMCI patients and the 17 controls. The neuropsychological findings were also compared between the subgroups. RESULTS: All the MCI patients showed decreased FA and increased MD in all the regions except the occipital areas. In the parietal regions and centrum semiovale, the vMCI patients had a greater FA decrease than the nvMCI patients and controls. In the hippocampi, the FA was lowest in the nvMCI patients. The memory function in the nvMCI patients was more impaired than that in the vMCI patients. The vMCI patients showed impairment of the visuospatial and frontal executive functions. CONCLUSION: We were able to correlate the microstructural alterations with the neuropsychological findings in the MCI subgroups.     

Diffusion tensor imaging in blepharospasm and blepharospasm-oromandibular dystonia

Patterns of white matter (WM) abnormalities and correlation with clinical features in patients with blepharospasm (BSP) and patients with blepharospasm-oromandibular dystonia (BOM) remain unknown. Using voxel-based analysis, diffusion behaviors of WM including fractional anisotropy (FA), mean diffusivity (MD) and eigenvalues were compared between 20 BSP patients vs. 11 healthy controls (HCs) and 11 patients with BOM vs. 11 HCs. Correlation analyses were performed to assess possible association between diffusion behaviors of significantly different areas and clinical measures. Compared with HCs, BSP patients showed significant FA reductions in the left anterior lobe of cerebellum. Significant increases of MD and radial diffusivity (RD) were detected in right lentiform nucleus and thalamus. Significantly decreased FA in the right precuneus of parietal lobe, increased MD in the right lentiform nucleus and insula, and increased axial diffusivity in the right insula were observed in BOM patients. The FA values in the WM of left cerebellum negatively correlated with disease severity in BSP patients measured by JRS (r = ?0.655, p = 0.002). The FA values in the right parietal WM negatively correlated with disease duration in BOM patients (r = ?0.745, p = 0.008). Both BSP and BOM are related to microstructural abnormalities of WM in the basal ganglia. WM changes outside the basal ganglia may present trait features that are specific for individual dystonia phenotype. The correlation between FA abnormalities and symptom severity suggests that DTI parameters might be of clinical value in assessing and following disability in BSP patients.     

Normal diffusivity of the domestic feline brain

Diffusion magnetic resonance imaging (MRI) provides useful information about neuroanatomy and improves detection of neuropathology. As yet, a comprehensive evaluation of the diffusivity parameters within the feline brain has not been documented. In this study, we anesthetized and performed in vivo MRI on the brain of eight neurologically normal felines. A T1-weighted structural sequence with a resolution of 0.5 mm³ and a parallel diffusion weighted sequence with 61 directions and a resolution of 1.5 mm³ was obtained. After correction and processing the diffusion brain data were parcellated into 151 regions of interest using previously published priors. These regions were grouped according to their lobar location within the brain (frontal, occipital, temporal, parietal, thalamus, midbrain, cerebellum, and white matter). The mean and standard deviation of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for these 151 individual regions and lobar groups were calculated and averaged across participants, creating a comprehensive distribution range of diffusion tensor values. When regions were statistically evaluated, white matter had significantly higher FA and RD and lower AD and MD diffusivity parameters when compared to other regions. Additionally, thalamic regions had significantly higher FA values than parietal and occipital regions. This information will not only help inform feline neuroanatomy but also will serve as a reference standard for future feline neuroimaging studies.     

Development of superficial white matter and its structural interplay with cortical gray matter in children and adolescents

Healthy human brain undergoes significant changes during development. The developmental trajectory of superficial white matter (SWM) is less understood relative to cortical gray matter (GM) and deep white matter. In this study, a multimodal imaging strategy was applied to vertexwise map SWM microstructure and cortical thickness to characterize their developmental pattern and elucidate SWM‐GM associations in children and adolescents. Microscopic changes in SWM were evaluated with water diffusion parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in 133 healthy subjects aged 10–18 years. Results demonstrated distinct maturational patterns in SWM and GM. SWM showed increasing FA and decreasing MD and RD underneath bilateral motor sensory cortices and superior temporal auditory cortex, suggesting increasing myelination. A second developmental pattern in SWM was increasing FA and AD in bilateral orbitofrontal regions and insula, suggesting improved axonal coherence. These SWM patterns diverge from the more widespread GM maturation, suggesting that cortical thickness changes in adolescence are not explained by the encroachment of SWM myelin into the GM‐WM boundary. Interestingly, age‐independent intrinsic association between SWM and cortical GM seems to follow functional organization of polymodal and unimodal brain regions. Unimodal sensory areas showed positive correlation between GM thickness and FA whereas polymodal regions showed negative correlation. Axonal coherence and differences in interstitial neuron composition between unimodal and polymodal regions may account for these SWM‐GM association patterns. Intrinsic SWM‐GM relationships unveiled by neuroimaging in vivo can be useful for examining psychiatric disorders with known WM/GM disturbances. Hum Brain Mapp 35:2806–2816, 2014. © 2013 Wiley Periodicals, Inc .     

Representation and propagation of epileptic activity in absences and generalized photoparoxysmal responses

Although functional imaging studies described networks associated with generalized epileptic activity, propagation patterns within these networks are not clear. In this study, electroencephalogram (EEG)‐based coherent source imaging dynamic imaging of coherent sources (DICS) was applied to different types of generalized epileptiform discharges, namely absence seizures (10 patients) and photoparoxysmal responses (PPR) (eight patients) to describe the representation and propagation of these discharges in the brain. The results of electrical source imaging were compared to EEG‐functional magnetic resonance imaging (fMRI) which had been obtained from the same data sets of simultaneous EEG and fMRI recordings. Similar networks were described by DICS and fMRI: (1) absence seizures were associated with thalamic involvement in all patients. Concordant results were also found for brain areas of the default mode network and the occipital cortex. (2) Both DICS and fMRI identified the occipital, parietal, and the frontal cortex in a network associated with PPR. (3) However, only when PPR preceded a generalized tonic‐clonic seizure, the thalamus was involved in the generation of PPR as shown by both imaging techniques. Partial directed coherence suggested that during absences, the thalamus acts as a pacemaker while PPR could be explained by a cortical propagation from the occipital cortex via the parietal cortex to the frontal cortex. In conclusion, the electrical source imaging is not only able to describe similar neuronal networks as revealed by fMRI, including deep sources of neuronal activity such as the thalamus, but also demonstrates interactions interactions within these networks and sheds light on pathogenetic mechanisms of absence seizures and PPR. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Diffusion and volumetry abnormalities in subcortical nuclei of patients with absence seizures

Purpose: The thalamus and basal ganglia play an important role in the propagation and modulation of generalized spike and slow‐wave discharges (SWDs) in absence epilepsy. Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique sensitive to microstructural abnormalities of cerebral tissue by quantification of diffusion parameter. The purpose of this study is to investigate the diffusion and volume changes in the basal ganglia and thalamus of patients with absence seizures. Methods: In 11 patients with absence seizures and 11 controls, the thalamus, caudate nucleus, putamen, and pallidum were segmented using an automated atlas‐based method on the DTI and three‐dimensional (3D) anatomic T₁‐weighted images. Then the fractional anisotropy (FA), mean diffusivity (MD), and volume were extracted and quantified. Key Findings: Compared with controls, patients reveal increased MD values bilaterally in thalamus, putamen, and left caudate nucleus; increased FA value in bilateral caudate nuclei; and loss of volume in bilateral thalamus, putamen, and pallidum. Significant correlations were observed between age of onset and diffusion parameter alterations in caudate nucleus or putamen. Significance: These findings provide preliminary evidence demonstrating that microstructural changes of subcortical structures are related to the chronic abnormal epileptic activity, and add further evidence for the involvement of thalamus and basal ganglia in propagation and modulation of SWDs in absence epilepsy. These results also indicate that DTI is more sensitive for detection of abnormal structure than the conventional MRI, and it may be adopted as a noninvasive means to understand the pathophysiologic evolution of absence seizures.     

Altered white matter structure in the visual system following early monocular enucleation

Partial visual deprivation from early monocular enucleation (the surgical removal of one eye within the first few years of life) results in a number of long‐term morphological adaptations in adult cortical and subcortical visual, auditory, and multisensory brain regions. In this study, we investigated whether early monocular enucleation also results in the altered development of white matter structure. Diffusion tensor imaging and probabilistic tractography were performed to assess potential differences in visual system white matter in adult participants who had undergone early monocular enucleation compared to binocularly intact controls. To examine the microstructural properties of these tracts, mean diffusion parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were extracted bilaterally. Asymmetries opposite to those observed in controls were found for FA, MD, and RD in the optic radiations, the projections from primary visual cortex (V1) to the lateral geniculate nucleus (LGN), and the interhemispheric V1 projections of early monocular enucleation participants. Early monocular enucleation was also associated with significantly lower FA bidirectionally in the interhemispheric V1 projections. These differences were consistently greater for the tracts contralateral to the enucleated eye, and are consistent with the asymmetric LGN volumes and optic tract diameters previously demonstrated in this group of participants. Overall, these results indicate that early monocular enucleation has long‐term effects on white matter structure in the visual pathway that results in reduced fiber organization in tracts contralateral to the enucleated eye. Hum Brain Mapp 39:133–144, 2018. © 2017 Wiley Periodicals, Inc.     

Callosal degeneration topographically correlated with cognitive function in amnestic mild cognitive impairment and alzheimer's disease dementia

Degeneration of the corpus callosum (CC) is evident in the pathogenesis of Alzheimer's disease (AD). However, the correlation of microstructural damage in the CC on the cognitive performance of patients with amnestic mild cognitive impairment (aMCI) and AD dementia is undetermined. We enrolled 26 normal controls, 24 patients with AD dementia, and 40 single‐domain aMCI patients with at least grade 1 hippocampal atrophy and isolated memory impairment. Diffusion tensor imaging (DTI) with fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (DA), and radial diffusivity (DR) were measured. The entire CC was parcellated based on fiber trajectories to specific cortical Brodmann areas using a probabilistic tractography method. The relationship between the DTI measures in the subregions of the CC and cognitive performance was examined. Although the callosal degeneration in the patients with aMCI was less extended than in the patients with AD dementia, degeneration was already exhibited in several subregions of the CC at the aMCI stage. Scores of various neuropsychological tests were correlated to the severity of microstructural changes in the subregional CC connecting to functionally corresponding cortical regions. Our results confirm that CC degeneration is noticeable as early as the aMCI stage of AD and the disconnection of the CC subregional fibers to the corresponding Brodmann areas has an apparent impact on the related cognitive performance. Hum Brain Mapp 35:1529–1543, 2014. © 2013 Wiley Periodicals, Inc.     

Rostral brain axonal injury in congenital central hypoventilation syndrome

Brain injury underlying the state‐related loss of ventilatory drive, autonomic, cognitive, and affective deficits in congenital central hypoventilation syndrome (CCHS) patients appears throughout the brain, as demonstrated by magnetic resonance (MR) T2 relaxometry and mean diffusivity studies. However, neither MR measure is optimal to describe types of axonal injury essential for assessing neural interactions responsible for CCHS characteristics. To evaluate axonal integrity and partition the nature of tissue damage (axonal vs. myelin injury) in CCHS, we measured water diffusion parallel (axial diffusivity) and perpendicular (radial diffusivity) to rostral brain fibers, indicative of axonal and myelin changes, respectively, with diffusion tensor imaging (DTI). We performed DTI in 12 CCHS (age 18.5 ± 4.9 years, 7 male) and 30 control (17.7 ± 4.6 years, 18 male) subjects, using a 3.0‐Tesla MR imaging scanner. Axial and radial diffusivity maps were calculated, spatially normalized, smoothed, and compared between groups (analysis of covariance; covariates, age and gender). Significantly increased radial diffusivity, primarily indicative of myelin injury, emerged in fibers of the corona radiata, internal capsule, corpus callosum, hippocampus through the fornix, cingulum bundle, and temporal and parietal lobes. Increased axial diffusivity, suggestive of axonal injury, appeared in fibers of the internal capsule, thalamus, corona radiata, and occipital and temporal lobes. Multiple brain regions showed both higher axial and radial diffusivity, indicative of loss of tissue integrity with a combination of myelin and axonal injury, including basal ganglia, bed nucleus, and limbic, occipital, and temporal areas. The processes underlying injury are unclear, but likely stem from both hypoxic and developmental processes. © 2010 Wiley‐Liss, Inc.     

A multiparametric evaluation of regional brain damage in patients with primary progressive multiple sclerosis

The purpose of this study is to define the topographical distribution of gray matter (GM) and white matter (WM) damage in patients with primary progressive multiple sclerosis (PPMS), using a multiparametric MR‐based approach. Using a 3 Tesla scanner, dual‐echo, 3D fast‐field echo (FFE), and diffusion tensor (DT) MRI scans were acquired from 18 PPMS patients and 17 matched healthy volunteers. An optimized voxel‐based (VB) analysis was used to investigate the patterns of regional GM density changes and to quantify GM and WM diffusivity alterations of the entire brain. In PPMS patients, GM atrophy was found in the thalami and the right insula, while mean diffusivity (MD) changes involved several cortical‐subcortical structures in all cerebral lobes and the cerebellum. An overlap between decreased WM fractional anisotropy (FA) and increased WM MD was found in the corpus callosum, the cingulate gyrus, the left short temporal fibers, the right short frontal fibers, the optic radiations, and the middle cerebellar peduncles. Selective MD increase, not associated with FA decrease, was found in the internal capsules, the corticospinal tracts, the superior longitudinal fasciculi, the fronto‐occipital fasciculi, and the right cerebral peduncle. A discrepancy was found between regional WM diffusivity changes and focal lesions because several areas had DT MRI abnormalities but did not harbor T2‐visible lesions. Our study allowed to detect tissue damage in brain areas associated with motor and cognitive functions, which are known to be impaired in PPMS patients. Combining regional measures derived from different MR modalities may be a valuable tool to improve our understanding of PPMS pathophysiology. Hum Brain Mapp 2009. © 2009 Wiley‐Liss, Inc.     

Increased cortical BOLD signal anticipates generalized spike and wave discharges in adolescents and adults with idiopathic generalized epilepsies

Purpose: Electroencephalography–functional magnetic resonance imaging (EEG‐fMRI) coregistration has recently revealed that several brain structures are involved in generalized spike and wave discharges (GSWDs) in idiopathic generalized epilepsies (IGEs). In particular, deactivations and activations have been observed within the so‐called brain default mode network (DMN) and thalamus, respectively. In the present study we analyzed the dynamic time course of blood oxygen level–dependent (BOLD) changes preceding and following 3 Hz GSWDs in a group of adolescent and adult patients with IGE who presented with absence seizures (AS). Our aim was to evaluate cortical BOLD changes before, during, and after GSWD onset. Methods: Twenty‐one patients with IGE underwent EEG‐fMRI coregistration. EEG‐related analyses were run both at the single‐subject and at group level (random effect). The time‐course analysis was conducted for 3 s time windows before, during, and after GSWDs, and they were included until no further BOLD signal changes were observed. Key Findings: Fifteen patients (nine female, mean age 28 years) had GSWDs during EEG‐fMRI coregistration (262 total events, mean duration 4 s). Time‐course group analysis showed BOLD increments starting approximately 10 s before GSWD onset located in frontal and parietal cortical areas, and especially in the precuneus‐posterior cingulate region. At GSWD onset, BOLD increments were located in thalamus, cerebellum, and anterior cingulate gyrus, whereas BOLD decrements were observed in the DMN regions persisting until 9 s after onset. Significance: Hemodynamic changes (BOLD increments) occurred in specific cortical areas, namely the precuneus/posterior cingulate, lateral parietal, and frontal cortices, several seconds before EEG onset of GSWD. A dysfunction of these brain regions, some of which belongs to the DMN, may be crucial in generating GSWDs in patients with IGE.     

White‐matter abnormalities in attention deficit hyperactivity disorder: A diffusion tensor imaging study

Current evidence suggests that attention deficit hyperactivity disorder (ADHD) involves dysfunction in wide functional networks of brain areas associated with attention and cognition. This study examines the structural integrity of white‐matter neural pathways, which underpin these functional networks, connecting fronto‐striatal and fronto‐parietal circuits, in children with ADHD. Fifteen right‐handed 8 to 18‐year‐old males with ADHD‐combined type and 15 right‐handed, age, verbal, and performance IQ‐matched, healthy males underwent diffusion tensor imaging. A recent method of tract‐based spatial statistics was used to examine fractional anisotropy (FA) and mean diffusivity within major white‐matter pathways throughout the whole‐brain. White‐matter abnormalities were found in several distinct clusters within left fronto‐temporal regions and right parietal‐occipital regions. Specifically, participants with ADHD showed greater FA in white‐matter regions underlying inferior parietal, occipito‐parietal, inferior frontal, and inferior temporal cortex. Secondly, eigenvalue analysis suggests that the difference in FA in ADHD may relate to a lesser degree of neural branching within key white‐matter pathways. Tractography methods showed these regions to generally form part of white‐matter pathways connecting prefrontal and parieto‐occipital areas with the striatum and the cerebellum. Our findings demonstrate anomalous white‐matter development in ADHD in distinct cortical regions that have previously been shown to be dysfunctional or hypoactive in fMRI studies of ADHD. These data add to an emerging picture of abnormal development within fronto‐parietal cortical networks that may underpin the cognitive and attentional disturbances associated with ADHD. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.     

Diffusion tensor quantification of the relations between microstructural and macrostructural indices of white matter and reading

Few researchers agree about the relationship between fronto–temporo–parietal white matter microstructure and reading skills. Unlike many previous reports, which only measured fractional anisotropy, we have also measured macroscopic volume (regional white matter tract volume) and three microstructural indices (axial, radial, and mean diffusivity) to increase interpretability of our findings. We examined the reading‐related skills and white matter structure in 10 adolescents and adults with a history of poor reading and 20 age‐matched typical readers. We applied a diffusion tensor imaging atlas‐based algorithm to major white matter pathways. The relation of white matter structural indices to reading group, hemisphere, and reading‐related skill was analyzed using linear models. White matter microstructural indices were related to performance on a sublexical decoding task, but the relations between particular microstructural indices and sublexical decoding ability and reading group were different for association (i.e., cortical–cortical) and projection (i.e., subcortical–cortical) white matter pathways. Changes in projection pathways were consistent with alterations in white matter organization and axonal size, whereas changes in association pathways were consistent with alternations in pathway complexity. Changes in macrostructure paralleled changes in microstructure. We conclude that the relations between several microstructural indices and factors related to reading ability are different for association and projection pathways. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

Diffusion imaging studies of Huntington's disease: A meta-analysis

BackgroundDiffusion tensor imaging (DTI) could detect abnormal brain microstructural alterations. DTI studies of Huntington's Disease(HD) have yielded inconsistent results.ObjectiveTo integrate the existing DTI studies of HD and explore the validity of DTI to detect microstructural damages in HD brain via meta-analysis.MethodsSystematic and comprehensive searches of the databases were performed for DTI studies of HD. The data from the studies that met our inclusion criteria were extracted and analyzed using the CMA2 software. Random effect models were utilized to minimize the potential between-study heterogeneity. One-way sensitivity analysis was conducted to test the robustness of the results.ResultsThe meta-analysis included 140 pre-symptomatic HD (PreHD), 235 symptomatic HD (SymHD) patients and 302 controls, revealing significantly increased fractional anisotropy (FA) in the caudate, putamen, and globus pallidus, while decreased FA in the corpus callosum of both PreHD and SymHD patients compared with controls. In addition, significantly increased mean diffusivity (MD) was identified in the putamen and thalamus of both PreHD and SymHD patients, and in the caudate of SymHD patients, while no significant difference in MD in the caudate of PreHD patients. In the corpus callosum, there was a significant increase of radial diffusivity and axial diffusivity in SymHD patients compared with controls. Meta-regression showed gender-based difference in MD values of the caudate.ConclusionsOur meta-analysis provides further evidence that DTI detects microstructural damage of both white matter and gray matter even in PreHD gene carriers. MD is less sensitive than FA in detecting structural changes in PreHD.     

Subcortical microstructural diffusion changes correlate with gait impairment in Parkinson's disease

BackgroundGait impairments are common in Parkinson's Disease (PD) and are likely caused by degeneration in multiple brain circuits, including the basal ganglia, thalamus and mesencephalic locomotion centers (MLC). Diffusion tensor imaging (DTI) assesses fractional anisotropy (FA) and mean diffusivity (MD) that reflect the integrity of neuronal microstructure. We hypothesized that DTI changes in motor circuits correlate with gait changes in PD.ObjectiveWe aimed to identify microstructural changes of brain locomotion control centers in PD via DTI and their correlations with clinical and quantitative measures of gait.MethodsTwenty-one PD patients reporting gait impairment and 15 controls were recruited. Quantitative gait and clinical tests were recorded in PD subjects’ medication ON and OFF states. Region of Interest (ROI) analysis of the thalamus, basal ganglia and MLC was performed using ExploreDTI. Correlations between FA/MD with clinical gait parameters were examined.ResultsMicrostructural changes were seen in the thalamus, caudate and MLC in the PD compared to the control group. Thalamic microstructural changes significantly correlated with gait parameters in the pace domain including the Timed Up and Go in the ON state. Caudate changes correlated with cadence and stride time in the OFF state.ConclusionsOur pilot study suggests that PD is associated with a characteristic regional pattern of microstructural degradation in the thalamus, caudate and MLC. The DTI changes may represent subcortical locomotion network failure. Overall, DTI ROI analyses might provide a useful tool for assessing PD for functional status and specific motor domains, such as gait, and potentially could serve as an imaging marker.     

Diffusion tensor imaging of the brain

Diffusion tensor imaging (DTI) is a promising method for characterizing microstructural changes or differences with neuropathology and treatment. The diffusion tensor may be used to characterize the magnitude, the degree of anisotropy, and the orientation of directional diffusion. This review addresses the biological mechanisms, acquisition, and analysis of DTI measurements. The relationships between DTI measures and white matter pathologic features (e.g., ischemia, myelination, axonal damage, inflammation, and edema) are summarized. Applications of DTI to tissue characterization in neurotherapeutic applications are reviewed. The interpretations of common DTI measures (mean diffusivity, MD; fractional anisotropy, FA; radial diffusivity, D _r; and axial diffusivity, D _a) are discussed. In particular, FA is highly sensitive to microstructural changes, but not very specific to the type of changes (e.g., radial or axial). To maximize the specificity and better characterize the tissue microstructure, future studies should use multiple diffusion tensor measures (e.g., MD and FA, or D _a and D _r).     

Free water elimination improves test–retest reproducibility of diffusion tensor imaging indices in the brain: A longitudinal multisite study of healthy elderly subjects

Free water elimination (FWE) in brain diffusion MRI has been shown to improve tissue specificity in human white matter characterization both in health and in disease. Relative to the classical diffusion tensor imaging (DTI) model, FWE is also expected to increase sensitivity to microstructural changes in longitudinal studies. However, it is not clear if these two models differ in their test–retest reproducibility. This study compares a bi‐tensor model for FWE with DTI by extending a previous longitudinal‐reproducibility 3T multisite study (10 sites, 7 different scanner models) of 50 healthy elderly participants (55–80 years old) scanned in two sessions at least 1 week apart. We computed the reproducibility of commonly used DTI metrics (FA: fractional anisotropy, MD: mean diffusivity, RD: radial diffusivity, and AXD: axial diffusivity), derived either using a DTI model or a FWE model. The DTI metrics were evaluated over 48 white‐matter regions of the JHU‐ICBM‐DTI‐81 white‐matter labels atlas, and reproducibility errors were assessed. We found that relative to the DTI model, FWE significantly reduced reproducibility errors in most areas tested. In particular, for the FA and MD metrics, there was an average reduction of approximately 1% in the reproducibility error. The reproducibility scores did not significantly differ across sites. This study shows that FWE improves sensitivity and is thus promising for clinical applications, with the potential to identify more subtle changes. The increased reproducibility allows for smaller sample size or shorter trials in studies evaluating biomarkers of disease progression or treatment effects. Hum Brain Mapp 38:12–26, 2017. © 2016 Wiley Periodicals, Inc.     

Development of short‐range white matter in healthy children and adolescents

Neural communication is facilitated by intricate networks of white matter (WM) comprised of both long and short range connections. The maturation of long range WM connections has been extensively characterized, with projection, commissural, and association tracts showing unique trajectories with age. There, however, remains a limited understanding of age‐related changes occurring within short range WM connections, or U‐fibers. These connections are important for local connectivity within lobes and facilitate regional cortical function and greater network economy. Recent studies have explored the maturation of U‐fibers primarily using cross‐sectional study designs. Here, we analyzed diffusion tensor imaging (DTI) data for healthy children and adolescents in both a cross‐sectional (n = 78; mean age = 13.04 ± 3.27 years) and a primarily longitudinal (n = 26; mean age = 10.78 ± 2.69 years) cohort. We found significant age‐related differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) across the frontal, parietal, and temporal lobes of participants within the cross‐sectional cohort. By contrast, we report significant age‐related differences in only FA for participants within the longitudinal cohort. Specifically, larger FA values were observed with age in frontal, parietal, and temporal lobes of the left hemisphere. Our results extend previous findings restricted to long range WM to demonstrate regional changes in the microstructure of short range WM during childhood and adolescence. These changes possibly reflect continued myelination and axonal organization of short range WM with increasing age in more anterior regions of the left hemisphere. Hum Brain Mapp 39:204–217, 2018. © 2017 Wiley Periodicals, Inc.     

Brain white matter microstructure is associated with susceptibility to motion‐induced nausea

Nausea is associated with significant morbidity, and there is a wide range in the propensity of individuals to experience nausea. The neural basis of the heterogeneity in nausea susceptibility is poorly understood. Our previous functional magnetic resonance imaging (fMRI) study in healthy adults showed that a visual motion stimulus caused activation in the right MT+/V5 area, and that increased sensation of nausea due to this stimulus was associated with increased activation in the right anterior insula. For the current study, we hypothesized that individual differences in visual motion‐induced nausea are due to microstructural differences in the inferior fronto‐occipital fasciculus (IFOF), the white matter tract connecting the right visual motion processing area (MT+/V5) and right anterior insula. To test this hypothesis, we acquired diffusion tensor imaging data from 30 healthy adults who were subsequently dichotomized into high and low nausea susceptibility groups based on the Motion Sickness Susceptibility Scale. We quantified diffusion along the IFOF for each subject based on axial diffusivity (AD); radial diffusivity (RD), mean diffusivity (MD) and fractional anisotropy (FA), and evaluated between‐group differences in these diffusion metrics. Subjects with high susceptibility to nausea rated significantly (P < 0.001) higher nausea intensity to visual motion stimuli and had significantly (P < 0.05) lower AD and MD along the right IFOF compared to subjects with low susceptibility to nausea. This result suggests that differences in white matter microstructure within tracts connecting visual motion and nausea‐processing brain areas may contribute to nausea susceptibility or may have resulted from an increased history of nausea episodes.