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The mammillary bodies as part of the hypothalamic nuclei are in the central limbic circuitry of the human brain. The mammillary bodies are shown to be directly or indirectly connected to the amygdala, hippocampus, and thalami as the major gray matter structures of the human limbic system. Although it is not primarily considered as part of the human limbic system, the thalamus is shown to be involved in many limbic functions of the human brain. The major direct connection of the thalami with the hypothalamic nuclei is known to be through the mammillothalamic tract. Given the crucial role of the mammillothalamic tracts in memory functions, diffusion tensor imaging may be helpful in better visualizing the surgical anatomy of this pathway noninvasively. This study aimed to investigate the utility of high spatial resolution diffusion tensor tractography for mapping the trajectory of the mammillothalamic tract in the human brain. Fifteen healthy adults were studied after obtaining written informed consent. We used high spatial resolution diffusion tensor imaging data at 3.0 T. We delineated, for the first time, the detailed trajectory of the mammillothalamic tract of the human brain using deterministic diffusion tensor tractography.

Diagnosis, clinical management and research of psychiatric disorders remain subjective - largely guided by historically developed categories which may not effectively capture underlying pathophysiological mechanisms of dysfunction. Here, we report a novel approach of identifying and validating distinct and biologically meaningful clinical phenotypes of bipolar disorders using both unsupervised and supervised machine learning techniques. First, neurocognitive data were analyzed using an unsupervised machine learning approach and two distinct clinical phenotypes identified namely; phenotype I and phenotype II. Second, diffusion weighted imaging scans were pre-processed using the tract-based spatial statistics (TBSS) method and 'skeletonized' white matter fractional anisotropy (FA) and mean diffusivity (MD) maps extracted. The 'skeletonized' white matter FA and MD maps were entered into the Elastic Net machine learning algorithm to distinguish individual subjects' phenotypic labels (e.g. phenotype I vs. phenotype II). This calculation was performed to ascertain whether the identified clinical phenotypes were biologically distinct. Original neurocognitive measurements distinguished individual subjects' phenotypic labels with 94% accuracy (sensitivity=92%, specificity=97%). TBSS derived FA and MD measurements predicted individual subjects' phenotypic labels with 76% and 65% accuracy respectively. In addition, individual subjects belonging to phenotypes I and II were distinguished from healthy controls with 57% and 92% accuracy respectively. Neurocognitive task variables identified as most relevant in distinguishing phenotypic labels included; Affective Go/No-Go (AGN), Cambridge Gambling Task (CGT) coupled with inferior fronto-occipital fasciculus and callosal white matter pathways. These results suggest that there may exist two biologically distinct clinical phenotypes in bipolar disorders which can be identified from healthy controls with high accuracy and at an individual subject level. We suggest a strong clinical utility of the proposed approach in defining and validating biologically meaningful and less heterogeneous clinical sub-phenotypes of major psychiatric disorders., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Previous studies have reported abnormalities of white-matter diffusivity in pediatric bipolar disorder. However, it has not been established whether these abnormalities are able to distinguish individual subjects with pediatric bipolar disorder from healthy controls with a high specificity and sensitivity. Diffusion-weighted imaging scans were acquired from 16 youths diagnosed with DSM-IV bipolar disorder and 16 demographically matched healthy controls. Regional white matter tissue microstructural measurements such as fractional anisotropy, axial diffusivity and radial diffusivity were computed using an atlas-based approach. These measurements were used to 'train' a support vector machine (SVM) algorithm to predict new or 'unseen' subjects' diagnostic labels. The SVM algorithm predicted individual subjects with specificity=87.5%, sensitivity=68.75%, accuracy=78.12%, positive predictive value=84.62%, negative predictive value=73.68%, area under receiver operating characteristic curve (AUROC)=0.7812 and chi-square p-value=0.0012. A pattern of reduced regional white matter fractional anisotropy was observed in pediatric bipolar disorder patients. These results suggest that atlas-based diffusion weighted imaging measurements can distinguish individual pediatric bipolar disorder patients from healthy controls. Notably, from a clinical perspective these findings will contribute to the pathophysiological understanding of pediatric bipolar disorder., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Prospective motion correction methods using an optical system, diffusion-weighted prospective acquisition correction, or a free induction decay navigator have recently been applied to correct for motion in diffusion tensor imaging. These methods have some limitations and drawbacks. This article describes a novel technique using a three-dimensional-echo planar imaging navigator, of which the contrast is independent of the b-value, to perform prospective motion correction in diffusion weighted images, without having to reacquire volumes during which motion occurred, unless motion exceeded some preset thresholds. Water phantom and human brain data were acquired using the standard and navigated diffusion sequences, and the mean and whole brain histogram of the fractional anisotropy and mean diffusivity were analyzed. Our results show that adding the navigator does not influence the diffusion sequence. With head motion, the whole brain histogram-fractional anisotropy shows a shift toward lower anisotropy with a significant decrease in both the mean fractional anisotropy and the fractional anisotropy histogram peak location (P<0.01), whereas the whole brain histogram-mean diffusivity shows a shift toward higher diffusivity with a significant increase in the mean diffusivity (P<0.01), even after retrospective motion correction. These changes in the mean and the shape of the histograms are recovered substantially in the prospective motion corrected data acquired using the navigated sequence., (Copyright © 2012 Wiley Periodicals, Inc.)

Purpose: To investigate the utility of diffusion tensor tractography at 1mm slice thickness to map and quantify the whole trajectory of different cortico-ponto-cerebellar pathways of the healthy adult human brain., Materials and Methods: This work was approved by the local Institutional Review Board, and was Health Insurance Portability and Accountability Act (HIPAA) compliant. Five healthy right-handed men (age range, 24-37 years) were studied and written informed consent was obtained. Diffusion tensor imaging data acquired with 1-mm slice thickness at a 3.0 Tesla (T) clinical MRI scanner were prepared and analyzed using tractography methods to reconstruct the cortico-ponto-cerebellar pathways which included the fronto-ponto-cerebellar, parieto-ponto-cerebellar, occipito-ponto-cerebellar, and temporo-ponto-cerebellar tracts., Results: We demonstrate the feasibility of tractographic mapping and quantification of the four cortico-ponto-cerebellar system components based on their cortical connections in the healthy human brain using DTI data with thin 1-mm sections., Conclusion: In vivo quantification of different cortico-ponto-cerebellar pathways based on cortical connection is feasible, using 1-mm slices at 3.0T.

Using diffusion tensor tractography, we quantified the microstructural changes in the association, projection, and commissural compact white matter pathways of the human brain over the lifespan in a cohort of healthy right-handed children and adults aged 6-68 years. In both males and females, the diffusion tensor radial diffusivity of the bilateral arcuate fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, corticospinal, somatosensory tracts, and the corpus callosum followed a U-curve with advancing age; fractional anisotropy in the same pathways followed an inverted U-curve. Our study provides useful baseline data for the interpretation of data collected from patients.

Recent studies demonstrated that diffusion tensor imaging (DTI) can provide information regarding white matter integrity of the corpus callosum (CC). In this study, DTI parameters were compared between cocaine dependent subjects (CDs) and non-drug using controls (NCs) in midsagittal CC. DTI images were acquired from 19 CDs and 18 age-matched NCs. The midsagittal CC was segmented into: genu, rostral body, anterior midbody, posterior midbody, isthmus, and splenium. Linear mixed models analyses showed that, relative to NCs, CDs had lower fractional anisotropy (FA), higher radial diffusivity (lambda(perpendicular)), and higher mean diffusivity (D(av)) in the isthmus; higher lambda(perpendicular) and D(av) in the rostral body; and lower FA in the splenium. After including mass of lifetime alcohol use in the mixed model analysis of covariance (ANCOVA) as a covariate, significant between group differences in lambda(perpendicular) in the rostral body and isthmus remained. These results suggest that alterations in lambda(perpendicular) in the rostral body and isthmus were mainly due to cocaine use, consistent with previous studies showing that cocaine may alter myelin integrity. Between group differences in FA in the isthmus and splenium, and D(av) in the rostral body and isthmus became non-significant after inclusion of alcohol use as a covariate. This is suggestive of alcohol influencing these values, or may be related to the decreased degrees of freedom for these effects. Consistent with clinical data of greater severity of drug use in smoked versus intranasal cocaine, subjects who smoked cocaine showed lower FA and higher lambda(perpendicular) compared to intranasal CDs.

The mapping of the human brain white matter fiber networks relative to deep subcortical and cortical gray matter requires high spatial resolution which is challenged by the low signal-to-noise ratio. The purpose of this short report was to introduce a whole brain high spatial resolution diffusion tensor imaging (DTI) protocol that enabled for the first time the mapping of corticopontocerebellar, frontostriatal and thalamofrontal fiber pathways in addition to other limbic, commissural, association and projection white matter pathways relative to the segmented deep gray (e.g., caudate nuclei) and the cortical lobes. Our DTI acquisition protocol and analysis strategy provide important template for brain-behavior research and for teaching brain mapping and are clinically affordable for patient comfort.

Lack of adequate sensitivity and spatial resolution in previous noninvasive imaging studies has impeded the depiction of different somatosensory pathways (the medial lemniscus and spinal lemniscus). We investigated whether incorporation of diffusion tensor imaging (DTI) at high isotropic spatial resolution and DTI-based 3D fiber-tractography information can facilitate the study of anatomical parcellation of the somatosensory system in the healthy adult human brainstem. Five healthy men (age range 24-37 years) were studied, and written informed consent was obtained from all subjects. Three-Tesla MRI diffusion tensor tractography (DTT) using fiber assignment by the continuous tracking (FACT) approach at high spatial resolution was used to reconstruct three white matter tracts, the medial lemniscus (ML), spinal lemniscus (SL), and central tegmental tract (CTT), to delineate and quantify the sensory pathways within the brainstem. We demonstrate that these three pathways are distinguishable from each other. The tractographic patterns of the three pathways on all subjects were similar and consistent with atlases of anatomy. We also quantified the diffusion tensor metrics (fractional anisotropy and mean diffusivity) of the two somatosensory pathways, the SL and ML. The fractional anisotropy of the ML was significantly higher than that of the SL (p = 0.005) The average diffusivity was significantly smaller for the ML than for the SL (p = 0.003).

Diffuse axonal injury (DAI) that follows traumatic brain injury (TBI) is thought to be a major contributor to neurocognitive dysfunction that sometimes follows TBI. Conventional magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and neuropsychological tests (NPT) were performed on 38 TBI patients [hemorrhagic DAI (H-DAI, n=8), non-hemorrhagic (Nh-DAI, n=7), with no apparent DAI on conventional MRI (NA-DAI, n=23)] with a Glasgow Coma Scale score ranging between 9 and 13. The fractional anisotropy (FA) and mean diffusivity (MD) were quantified from different regions of the corpus callosum (CC), and peri-ventricular white matter (PWM) within 5-14 days and 6 months following TBI. Patients in all three groups showed decreased FA in the anterior limb of the internal capsule (ALIC) and the posterior limb of the internal capsule (PLIC), while the genu of the CC showed a decrease in the H-DAI group during the early period following TBI that persisted 6 months later, which appeared to be consistent with axonopathy. In patients without abnormalities on conventional MRI and DTI in the initial phase, a significant decrease in FA and increase in MD were observed in a few regions of the CC at 6 months, which was suggestive of demyelination/gliosis. The changes in FA and MD in the CC and PWM at 6 months follow-up showed significant correlation with some of the NPT performed in the three groups. DTI demonstrates axonopathy in the acute stage, as well as at secondary stages, at 6 months post-injury in the CC and PWM in regions of normal-appearing white matter on conventional MRI.

Purpose: To investigate the utility of caudate nuclei (CN) macro- and microstructural metrics as markers of gray matter degeneration in healthy adults and relapsing-remitting multiple sclerosis (RRMS) patients., Materials and Methods: The normal age- and pathology-related changes in caudate nuclei volume (CNV), the corresponding diffusion tensor metrics, and the T(2) relaxation times were measured in a cohort of 32 healthy adults (12 men/20 women; age range 21-59 years) and 32 age-matched RRMS patients (8 men/34 women; age range 21-57 years)., Results: Smaller values in both the absolute CNV and the caudate volume ratio relative to the total intracranial volume (CNVp) were observed in the RRMS group relative to healthy controls. The fractional anisotropy (FA), based on the diffusion tensor imaging (DTI) of the CN increased with age in healthy adults (r = 0.52; P = 0.003) but not in patients (r = 0.28; P = 0.12). The caudate FA value was approximately 9% larger in RRMS patients relative to controls (P = 0.001). The mean diffusivity of the CN was greater in the RRMS group compared to controls (P = 0.02). The caudate T(2) relaxation times were smaller in the RRMS group relative to the control group (3% reduction, P = 0.05). T(2) relaxation times did not exhibit age-related changes (P > 0.35) in either cohort. Strong and significant correlations between CNVp and whole-brain lesion load (r = -0.48; P = 0.005) and whole-brain CSF fraction (r = -0.46; P = 0.01) were also noted., Conclusion: These preliminary findings indicate that caudate DTI-derived metrics can serve as potential quantitative radiological markers of MS pathology.

The midsagittal corpus callosum (CC) cross-sectional area subdivisions have been used as early and sensitive markers of human brain white matter connectivity, development, natural aging and disease. Despite the simplicity and conspicuity of the appearance of the CC on anatomical magnetic resonance imaging (MRI), the published quantitative MRI literature on its regional sex and age trajectories are contradictory. The availability of noninvasive quantitative methods to assess the CC regions across the human lifespan would help clarify its contribution to behavior and cognition. In this report, we extended the utility of a recently described semi-automated diffusion tensor imaging (DTI) tissue segmentation method to utilize the high orientation contrast of the CC on DTI. Using optimized DTI methods on a cohort of 121 right-handed children and adults aged 6-68 years, we examined the CC areas and corresponding DTI metrics of the different functionally specialized sectors of the CC. Both the area and fractional anisotropy metrics followed inverted U-shaped curves, while the mean and radial diffusivities followed U-curves reflecting white matter progressive and regressive myelination dynamics that continue into young adulthood.

Object: Patients with spina bifida (SB) have variable intellectual outcomes. The authors used diffusion tensor (DT) imaging to quantify whole-brain volumes of gray matter, white matter, and cerebrospinal fluid (CSF), and perform regional quantitative microstructural assessments of gray matter nuclei and white matter tracts in relation to intellectual outcomes in patients with SB., Methods: Twenty-nine children with myelomeningoceles and 20 age- and sex-matched children with normal neural tube development underwent MR imaging with DT image acquisition and assessments of intelligence. The DT imaging-derived metrics were the fractional anisotropy (FA), axial (parallel), and transverse (perpendicular) diffusivities. These metrics were also used to segment the brain into white matter, gray matter, and CSF. A region-of-interest analysis was conducted of the white and gray matter structures implicated in hydrocephalus., Results: The amount of whole-brain gray matter was decreased in patients with SB, with a corresponding increase in CSF (p < 0.0001). Regional transverse diffusivity in the caudate nucleus was decreased (p < 0.0001), and the corresponding FA was increased (p < 0.0001), suggesting reduced dendritic branching and connectivity. Fractional anisotropy in the posterior limb of the internal capsule increased in the myelomeningocele group (p = 0.02), suggesting elimination of some divergent fascicles; in contrast, the FA in several white matter structures (such as the corpus callosum genu [p < 0.001] and arcuate fasciculus) was reduced, suggesting disruption of myelination. Diffusion tensor imaging-metrics involving gray matter volume and the caudate nucleus, but not other structures, predicted variations in IQ (r = 0.37-0.50; p < 0.05)., Conclusions: Diffusion tensor imaging-derived metrics provide noninvasive neuronal surrogate markers of the pathogenesis of SB and predict variations in general intellectual outcomes in children with this condition.

Purpose: To quantify microstructural abnormalities in the major association pathways of children affected by spina bifida myelomeningocele (SBM) and shunted hydrocephalus using whole-brain diffusion tensor imaging (DTI)., Materials and Methods: The institutional review board approved this Health Insurance Portability and Accountability Act (HIPAA)-compliant study and written informed consent/assent were obtained prior to the study. The 69 participants included 38 children with SBM and shunted hydrocephalus (age mean +/- SD = 12.30 +/- 2.10 years; 22 boys; 10 left-handed) and 31 age- and sex-matched normally-developing children (11.56 +/- 2.72 years; 15 boys, four left-handed). Diffusion tensor tractography (DTT) was performed to delineate and quantify bilaterally four major association pathways (arcuate, inferior longitudinal, inferior fronto-occipital, and uncinate fasciculi)., Results: The group with SBM did not exhibit the pattern of age-related decreases in the diffusivities observed in the controls. The transverse and axial diffusivities were significantly elevated in most of the white matter pathways of the participants with SBM. The fractional anisotropy (FA) was significantly lower in most of the association pathways. Many of the association pathways were not traceable in some participants with SBM compared to the controls at the selected FA thresholds., Conclusion: DTT revealed diffusion tensor characteristics of abnormal development (nonvisualization/poor visualization of tracts, downward arrow FA, upward arrow diffusivities), impairment in myelination (upward arrow transverse diffusivity) as well as abnormalities in intrinsic axonal characteristics and extraaxonal/extracellular space (upward arrow axial diffusivity) in the association pathways of the SBM children. The differences in the diffusion metrics observed in the children with SBM are suggestive of abnormal white matter development and persistent degeneration with increased age., ((c) 2008 Wiley-Liss, Inc.)

Purpose: To prospectively perform a direct measurement of fractional anisotropy (FA) and mean diffusivity (MD) in cortical lesions of patients with multiple sclerosis (MS)., Materials and Methods: The study was approved by the institutional review board and was HIPAA compliant; informed consent was obtained. Magnetic resonance (MR) images, including double inversion-recovery (DIR), phase-sensitive inversion-recovery (PSIR), and diffusion-tensor images, were acquired from nine MS patients with cortical lesions (five women, four men; median age, 47 years) and nine age- and sex-matched volunteer control subjects. Following nonlinear elastically constrained image registration for aligning diffusion-weighted images to DIR images, maps of FA and MD were computed for each subject. Cortical lesions were identified on DIR images and validated by using PSIR images. The diffusion-tensor imaging maps were then overlaid on the coregistered DIR images, and mean FA and MD values were measured in regions of interest drawn on the cortical lesions. Differences between normal gray matter (GM) and cortical lesions were evaluated by using the generalized estimating equation. FA and MD histograms of whole brain and GM (global analysis) in healthy control subjects and MS patients were also computed for comparison with those in previously published studies., Results: FA and MD values were significantly higher in cortical lesions compared with similar regions in healthy control subjects. Histogram peak FA was significantly decreased and peak MD was significantly increased in patients relative to control subjects., Conclusion: DIR and PSIR combined with nonlinear image registration allowed direct focal measurement of FA and MD in cortical lesions., ((c) RSNA, 2008.)

In this study of a cohort of 33 young and middle-age adults (19-59 years) we report simultaneous measurements of normal age-related changes in the caudate nuclei volume, diffusion tensor metrics, and T(2) relaxation time. Both the absolute caudate volume and its ratio relative to the total intracranial volume decreased rapidly with age in both men and women (r = -0.55; P < 0.001). The fractional diffusion tensor anisotropy of the caudate nuclei increased with age in both males and females (r = 0.48; P = 0.005). The corresponding age correlations of the caudate axial (r = 0.17; P = 0.35), transverse (r = -0.12; P = 0.50), mean diffusivities (r = 0.018; P = 0.92), and T(2) relaxation times (r = 0.194; P = 0.28) were weaker and did not reach statistical significance (P > 0.05). Our preliminary findings warrant further studies on the older and aging adults and indicate that caudate diffusion tensor imaging-derived metrics can be used as surrogates in modeling the neuronal substrates of gray matter atrophy., (2007 Wiley-Liss, Inc)

Whole-brain diffusion tensor tractography (DTT) at high signal-to-noise ratio and angular and spatial resolutions were utilized to study the effects of age, sex differences, and lateral asymmetries of 6 white matter pathways (arcuate fasciculus [AF], inferior longitudinal fasciculus, inferior fronto-occipital fasciculus [IFOF], uncinate fasciculus [UF], corticospinal tract [CST], and somatosensory pathway [SS]) in 31 right-handed children (6-17 years). Fractional anisotropy (FA), a measure of the orientational variance in water molecular diffusivity, and the magnitude of water diffusivity (parallel, perpendicular, and mean diffusivity) along the pathways were quantified. Three major patterns of maturation were observed: 1) significant increase in FA with age, accompanied by significant decreases in all 3 diffusivities (e.g., left IFOF); 2) significant decreases in all three diffusivities with age without significant changes in FA (e.g., left CST); and 3) no significant age-related changes in FA or diffusivity (e.g., SS). Sex differences were minimal. Many pathways showed lateral asymmetries. In the right hemisphere, the frontotemporal (FT) segment of AF was not visualized in a substantial (29%) number of participants. FA was higher in the left hemisphere in the FT segment of AF, UF, and CST, whereas it was lower in the frontoparietal segment of AF. This study provides normative data essential for the interpretation of pediatric brain DTT measurements in both health and disease.

We used a diffusion tensor imaging-based whole-brain tissue segmentation to characterize age-related changes in (a) whole-brain grey matter, white matter, and cerebrospinal fluid relative to intracranial volume and (b) the corresponding brain tissue microstructure using measures of diffusion tensor anisotropy and mean diffusivity. The sample, a healthy cohort of 119 right-handed males and females aged 7-68 years. Our results demonstrate that white matter and grey matter volumes and their corresponding diffusion tensor anisotropy and mean diffusivity follow nonlinear trajectories with advancing age. In contrast, cerebrospinal fluid volume increases linearly with age.

In this communication, a theoretical framework for quality control and parameter optimization in diffusion tensor imaging (DTI) is presented and validated. The approach is based on the analytical error propagation of the mean diffusivity (D(av)) obtained directly from the diffusion-weighted data acquired using rotationally invariant and uniformly distributed icosahedral encoding schemes. The error propagation of a recently described and validated cylindrical tensor model is further extrapolated to the spherical tensor case (diffusion anisotropy approximately 0) to relate analytically the precision error in fractional tensor anisotropy (FA) with the mean diffusion-to-noise ratio (DNR). The approach provided simple analytical and empirical quality control measures for optimization of diffusion parameter space in an isotropic medium that can be tested using widely available water phantoms.

Early diagnosis of Parkinson's disease (PD) is required to improve therapeutic responses. Indeed, a clinical diagnosis of resting tremor, rigidity, movement and postural deficiencies usually reflect >50% loss of the nigrostriatal system in disease. In a step to address this, quantitative diffusion tensor magnetic resonance imaging (DTI) was used to assess nigrostriatal degeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication model of dopaminergic nigral degeneration. We now demonstrate increased average diffusion (p<0.005) and decreased fractional anisotropy (p<0.03) in the substantia nigra (SN) of 5- to 7-day MPTP-treated animals when compared to saline controls. Transverse diffusivity demonstrated the most significant differences (p < or = 0.002) and correlated with the numbers of SN dopaminergic neurons (r=-0.75, p=0.012). No differences were found in the striatum, corpus callosum, cerebral cortex, or ventricles. These results demonstrate that DTI may be used as a surrogate biomarker of nigral dopaminergic neuronal degeneration.

Reduced fractional anisotropy (FA) in Diffusion Tensor Imaging (DTI) has been reported in cocaine dependent subjects compared to non-drug using controls. There are several pathological mechanisms that could be responsible for these findings, since FA can be reduced through damage to axonal tracts and by neuronal loss. One way of obtaining more information about pathology underlying changes in FA on DTI is diffusion tensor eigenvalues, representing diffusion along the fiber tract (lambda(1)) or perpendicular to the fiber tract (lambda(T)). Thirteen cocaine dependent subjects and 18 healthy controls underwent full brain DTI. Eigenvalues lambda(1) and lambda(T) of the corpus callosum were compared between cocaine users and controls. For lambda(T) there was a significant interaction of group x region of corpus callosum. Exploratory analysis of the subregions showed higher lambda(T) in the genu of the anterior corpus callosum of cocaine dependent subjects compared to control subjects. For lambda(1) there was no significant interaction of group x region of corpus callosum. Based on prior studies suggesting that alteration or damage to myelin increases diffusion perpendicular to the direction of fiber tracts (lambda(T)) with minimal effect on lambda(1) these findings are consistent with altered myelin in the corpus callosum in cocaine dependent subjects.

Background: Previous MRI studies of healthy children have reported age-related white matter (WM) changes in language and motor areas of the brain. The authors investigated WM development in healthy adolescent males through age-associated changes in fractional anisotropy (FA), radial (lambda( perpendicular)) and axial (lambda(||)) diffusivity., Methods: Twenty-four healthy adolescent males (mean age=16.6, SD=2.5 years) were divided into two groups with an age split of 16.9 years and underwent a whole-brain voxelwise analysis., Results: At a threshold of p<0.001 and extent threshold of 100 contiguous voxels, several clusters with increased FA and axial diffusivity and no differences in radial diffusivity were observed in older adolescents compared to the younger adolescents in the left arcuate fasciculus, bilateral posterior internal capsule/thalamic radiation, bilateral prefrontal gyrus, right superior temporal gyrus, and posterior corpus callosum. Increased FA and lambda(||) of several clusters along the arcuate fasciculus significantly correlated with a test of language and semantic memory., Conclusions: These results suggest ongoing maturational changes especially in the arcuate fasiculus during late adolescence. Increased FA and lambda(||) with no changes in radial diffusivity may reflect a developmental pattern of reduced tortuousity toward more straightened fibers and/or increased axonal fiber organization during late adolescence.

Diffusion Tensor Imaging (DTI) may provide information regarding effects of 3,4-methylenedioxymethamphetamine (MDMA) use on brain structure. Twelve MDMA users and 20 healthy controls underwent whole brain DTI data acquisition. Fractional anisotropy (FA), mean diffusivity (D(av)), and longitudinal (lambda(1)) and transverse (lambda(T)) diffusivities were compared between MDMA users and controls in 6 regions of the corpus callosum. MDMA users also completed the Barratt Impulsiveness Scale (BIS), and a subset of subjects completed the Iowa Gambling Task (IGT). Results showed significantly smaller lambda(1) in the rostral body of the corpus callosum in MDMA users, with no differences between groups on lambda(T), FA, or D(av). MDMA users also had a significantly higher BIS nonplanning score and greater preference for disadvantageous choices on the IGT. There was a significant positive correlation between lambda(1) in the rostral body of the corpus callosum and advantageous choices on the IGT. Further research on the etiology of these findings is warranted.

Purpose: To understand the biological basis of possible mechanisms responsible for increased fractional anisotropy (FA) in different stages of hemorrhage and hemorrhagic brain lesions., Materials and Methods: A total of 19 patients with cerebral hemorrhage (CH), five patients with hemorrhagic infarct (HI), and nine patients with hemorrhagic brain tumor (HBT) were prospectively evaluated with diffusion tensor imaging (DTI) and the FA and mean diffusivity (MD) was quantified. Ex vivo DTI of blood clot and histology of the blood clot and HBT were performed to interpret the temporal changes in the DTI metrics., Results: High FA (>0.20) with low MD in the acute and early subacute stage and low FA (<0.20) with increased MD in the late subacute and chronic stage of CH and HI were observed. HBT showed high FA with low MD at all stages. In CH and HI, a significant reduction in FA (P < 0.001) with increased MD (P < 0.001) was seen in the late subacute and chronic stages compared to the acute and early subacute stages, normal white matter (NWM), and HBT. In HBT, there was no significant statistical difference in the FA values between different stages. Histology of HBT and ex vivo blood clot showed structural organization of intact red blood cells (RBCs) with fibrin mesh where the FA values were high compared to normal tissue region that is devoid of blood., Conclusion: Intact RBCs entangled within fibrin mesh appear to be responsible for high FA in hemorrhagic brain lesions., ((c) 2006 Wiley-Liss, Inc.)

Purpose: To detect lesion-related focal Wallerian degeneration (WD) changes in different segments of the corpus callosum (CC) in patients with large middle cerebral arterial (MCA) territory stroke using diffusion tensor imaging (DTI)., Materials and Methods: Eight patients underwent DTI scans at three different time points: six to eight weeks, 10-12 weeks, and beyond six months of stroke onset. Eight healthy age-matched controls were also scanned using the same protocol at three different time points. Region-of-interest (ROI) analysis was performed on seven segments of the CC to determine the fractional anisotropy (FA), mean diffusivity (MD), and corresponding callosal cross-sectional areas., Results: On repeated-measures analysis of variance (ANOVA), a significant reduction in the FA values was observed from the first to the third study compared to controls, reflecting temporal degeneration in the rostrum, genu, rostral body, anterior midbody, and splenium of the CC. However, a significant temporal elevation in MD values was observed in only the rostral body and anterior midbody of the CC. This was associated with a significant region-specific reduction in the cross-sectional areas at time points beyond six months, and appears to be consistent with the loss of callosal structural components due to interruption of the cortico-callosal fibers secondary to WD., Conclusion: These results indicate that cortico-callosal topographical changes exhibit a significant temporal decline in observed FA values that is suggestive of cortico-callosal WD in patients with large MCA territory stroke.

A simple theoretical framework to compute the eigenvalues of a cylindrically symmetric prolate diffusion tensor (D) from one of the rotationally-invariant diffusion anisotropy indices and average diffusivity is presented and validated. Cylindrical or axial symmetry assumes a prolate ellipsoid shape (lambdaparallel=lambda1>lambdaperpendicular=(lambda2+lambda3)/2; lambda2=lambda3). A prolate ellipsoid with such symmetry is largely satisfied in a number of white matter (WM) structures, such as the spinal cord, corpus callosum, internal capsule, and corticospinal tract. The theoretical model presented is validated using in vivo DTI measurements of rat spinal cord and human brain, where eigenvalues were calculated from both the set of diffusion coefficients and a tensor analysis. This method was used to retrospectively analyze literature data that reported tensor-derived average diffusivity, anisotropy, and eigenvalues, and similar eigenvalue measurements were obtained. The method provides a means to retrospectively reanalyze literature data that do not report eigenvalues. Other potential applications of this method are also discussed., (Copyright (c) 2006 Wiley-Liss, Inc.)

Brain water may increase in hepatic encephalopathy (HE). Diffusion tensor imaging was performed in patients with cirrhosis with or without HE to quantify the changes in brain water diffusivity and to correlate it with neuropsychological (NP) tests. Thirty-nine patients with cirrhosis, with minimal (MHE) or overt HE, were studied and compared to 18 controls. Mean diffusivity (MD) and fractional anisotropy (FA) were calculated in corpus callosum, internal capsule, deep gray matter nuclei, periventricular frontal, and occipital white matter regions in both cerebral hemispheres. The MD and FA values from different regions in different groups were compared using analysis of variance and Spearman's rank correlation test. In 10 patients with MHE, repeat studies were performed after 3 weeks of lactulose therapy to look for any change in MD, FA, and NP scores. Significantly increased MD was found with insignificant changes in FA in various regions of brain in patients with MHE or HE compared with controls, indicating an increase in interstitial water in the brain parenchyma without any microstructural changes. A significant correlation was found between MD values from corpus callosum, internal capsule, and NP test scores. After therapy, MD values decreased significantly and there was a corresponding improvement in NP test scores. Further analysis showed that MD values were different for different grades of minimal or overt HE. In conclusion, the increase in MD with no concomitant changes in FA in cirrhosis with minimal or early HE indicates the presence of reversible interstitial brain edema.

In vivo longitudinal diffusion tensor imaging (DTI) of rodent spinal cord injury (SCI) was carried out over a period of eight weeks post-injury. A balanced, rotationally invariant, alternating gradient polarity icosahedral diffusion encoding scheme was used for an unbiased estimation of the DTI metrics. The fractional anisotropy (FA), diffusivities along (longitudinal), and perpendicular (transverse) to the fiber tracts, were estimated for the ventral, dorsal, and lateral white matter. In all the three regions, the DTI metrics were observed to be significantly different in injured cords relative to the uninjured controls close to the epicenter of the injury. However, these differences gradually disappeared away from the epicenter. The spatio-temporal changes in the DTI metrics showed a recovery pattern that is region specific. Although the temporal trends in the tissue recovery in rostral and caudal sections seem to be similar, overall the DTI metrics were observed to be closer to the normal tissue values in the caudal relative to the rostral sections (rostral-caudal asymmetry).

Purpose: The main objective of this study was to use diffusion tensor imaging (DTI) to search and quantify the extent of abnormality beyond the obvious lesions seen on the T2 and fluid-attenuation inversion recovery (FLAIR) magnetic resonance images in patients with chronic traumatic brain injury (TBI) with and without epilepsy., Methods: DTI was performed on 23 chronic TBI patients (with late posttraumatic epilepsy, n=14; without epilepsy, n=9) and 11 age-matched controls. The ratios of fractional anisotropy (FA) and mean diffusivity (MD) between the regions of interest beyond the T2/FLAIR-visualized abnormality and the corresponding contralateral normal-appearing region were calculated. FA and MD ratios were compared for relative changes in these parameters among the TBI subjects with and without epilepsy and controls. Tissue volumes exhibiting abnormalities on DTI also were measured in these patients., Results: The mean regional FA ratio was significantly lower, whereas the mean regional MD value was higher in patients with TBI compared with controls. The mean regional FA ratio was significantly lower in TBI patients with epilepsy (0.57+/-0.059) than in those without epilepsy (0.68+/-0.039). Although the regional MD ratio was higher in TBI patients with epilepsy (1.15+/-0.140) relative to those without epilepsy (1.09+/-0.141), the difference did not reach statistical significance. The tissue volume with low FA value also was found to be higher in TBI patients with epilepsy than without., Conclusions: Severity of injury as predicted by the DTI-derived increased volume of microstructure damage is associated with delayed posttraumatic epilepsy in TBI patients. These findings could be valuable in predicting epileptogenesis in patients with chronic TBI.

Diffusion tensor imaging (DTI) was performed on 15 fresh spontaneously or therapeutically aborted normal fetuses and five term infants at different gestational ages. Regional cortical fractional anisotropy (FA) values were observed to increase with gestational age (GA) from 15 to 28 weeks, followed by a decrease through 36 weeks. The early increase in the cortical FA value, which has never been reported before, is consistent with neuronal migration from the germinal matrix. A statistically significant inverse correlation between GA and the FA values in the germinal matrix was observed (r = -0.81, P = 0.004). In addition, there was a significant difference in the FA values in the right and left frontal cortices (P = 0.007, sign test), suggesting cortical lateralization during the early stage of development. Our studies suggest that the DTI-estimated anisotropy could be useful in following neuronal migration, cortical maturation, and associated changes in the germinal matrix during early brain development.

Purpose: To investigate the utility of whole-brain diffusion tensor imaging (DTI) in elucidating the pathogenesis of multiple sclerosis (MS) using the normal-appearing white matter (NAWM) of the corpus callosum (CC) as a marker of occult disease activity., Materials and Methods: A high signal-to-noise ratio (SNR) and optimized entire brain DTI data were acquired in 26 clinically-definite relapsing and remitting multiple sclerosis (RRMS) patients and 32 age-matched healthy adult controls. The fractional anisotropy (FA) values of seven functionally distinct regions in the normal-appearing CC were compared between patients and controls., Results: This study indicates that 1) there was a gender-independent FA heterogeneity of the functionally specialized CC segments in normal volunteers; 2) FA in the MS group was significantly decreased in the anterior (P=0.0039) and posterior (P=0.0018) midbody subdivisions of the CC, possibly due to a reduction of small-caliber axons; and 3) the FA of the genu of the CC was relatively intact in the MS patients compared to the healthy age-matched controls (P=0.644), while the splenium showed an insignificant trend of reduced FA values (P=0.248). The decrease in FA in any of the CC subdivisions did not correlate with disease duration (DD) or the expanded disability status scale (EDSS) score., Conclusion: The preliminary results are consistent with published histopathology and clinical studies on MS, but not with some published DTI reports. This study provides insights into the pathogenesis of MS, and the role played by compromised axonal integrity in this disease., (Copyright (c) 2005 Wiley-Liss, Inc.)

Regional values of fractional anisotropy (FA) and mean diffusivity (D(av)) of in vivo and excised rat spinal cords were measured using an iscosahedral encoding scheme that is based on 21 uniformly distributed and alternating gradient directions with an echo planar imaging (EPI) readout. Based on the water phantom studies, this scheme was shown to provide unbiased estimation of FA. The stability of the scanner during the acquisition of diffusion tensor imaging (DTI) data was evaluated. Repeated measurements of the FA values demonstrated excellent reproducibility, as assessed by the Bland-Altman analysis. These studies demonstrated a reduced anisotropy in excised samples relative to in vivo cords. Diffusion in the spinal cord gray matter was shown to be anisotropic. The FA value in the dorsal white matter (WM) was found to be higher relative to the ventral WM. Results from these studies should provide the necessary baseline data for serial in vivo DTI of injured spinal cord., (Copyright 2004 Wiley-Liss, Inc.)

Purpose: To categorize the varied appearances of tumor-altered white matter (WM) tracts on diffusion tensor eigenvector directional color maps., Materials and Methods: Diffusion tensor imaging (DTI) was obtained preoperatively in 13 patients with brain tumors ranging from benign to high-grade malignant, including primary and metastatic lesions, and maps of apparent diffusion coefficient (ADC), fractional anisotropy (FA), and major eigenvector direction were generated. Regions of interest (ROIs) were drawn within identifiable WM tracts affected by tumor, avoiding grossly cystic and necrotic regions, known fiber crossings, and gray matter. Patterns of WM tract alteration were categorized on the basis of qualitative analysis of directional color maps and correlation analysis of ADC and FA., Results: Four basic patterns of WM alteration were identified: 1) normal or nearly normal FA and ADC, with abnormal tract location or tensor directions attributable to bulk mass displacement, 2) moderately decreased FA and increased ADC with normal tract locations and tensor directions, 3) moderately decreased FA and increased ADC with abnormal tensor directions, and 4) near isotropy. FA and ADC were inversely correlated for Patterns 1-3 but did not discriminate edema from infiltrating tumor. However, in the absence of mass displacement, infiltrating tumor was found to produce tensor directional changes that were not observed with vasogenic edema, suggesting the possibility of discrimination on the basis of directional statistics., Conclusion: Tumor alteration of WM tracts tends to produce one of four patterns on FA and directional color maps. Clinical application of these patterns must await further study., (Copyright 2004 Wiley-Liss, Inc.)

Fractional anisotropy (FA) and relative anisotropy (RA) are the two most commonly used scalar measures of anisotropy in diffusion tensor (DT) MRI. While a few published studies have shown that FA has superior noise immunity relative to RA, no theoretical basis has been proposed to explain this behavior. In the current study, the diffusion tensor invariants were used to derive a simple analytical expression that directly relates RA and FA. An analysis based on that analytical expression demonstrated that the FA images have a higher signal-to-noise ratio (SNR) than RA for any value of tensor anisotropy RA or FA > 0. This theoretical behavior was verified using both Monte Carlo simulations and bootstrap analysis of DT-MRI data acquired in a spherical water phantom and normal human subjects., (Copyright 2004 Wiley-Liss, Inc.)

Abstract: In this work we provide an up-to-date short review of computational magnetic resonance imaging (MRI) and software tools that are widely used to process and analyze diffusion-weighted MRI data. A review of different methods used to acquire, model and analyze diffusion-weighted imaging data (DWI) is first provided with focus on diffusion tensor imaging (DTI). The major preprocessing, processing and post-processing procedures applied to DTI data are discussed. A list of freely available software packages to analyze diffusion MRI data is also provided. [Copyright &y& Elsevier]

Abstract: Analysis of crossing fibers is a challenging topic in recent diffusion-weighted imaging (DWI). Resolving crossing fibers is expected to bring major changes to present tractography results based on the standard tensor model. Model free approaches, like Q-ball or diffusion spectrum imaging, as well as multi-tensor models are used to unfold the different diffusion directions mixed in a voxel of DWI data. Due to its seeming simplicity, the two-tensor model (TTM) is applied frequently to provide two positive-definite tensors and the relative population fraction modeling two crossing fiber branches. However, problems with uniqueness and noise instability are apparent. To stabilize the fit, several of the 13 physical parameters are fixed ad hoc, before fitting the model to the data. Our analysis of the TTM aims at fitting procedures where ad hoc parameters are avoided. Revealing sources of instability, we show that the model''s inherent ambiguity can be reduced to one scalar parameter which only influences the fraction and the eigenvalues of the TTM, whereas the diffusion directions are not affected. Based on this, two fitting strategies are proposed: the parsimonious strategy detects the main diffusion directions without extra parameter fixation, to determine the eigenvalues and the population fraction an empirically motivated condition must be added. The expensive strategy determines all 13 physical parameters of the TTM by a fit to DWIs alone; no additional assumption is necessary. Ill-posedness of the model in case of noisy data is cured by denoising of the data and by L-curve regularization combined with global minimization performing a least-squares fit of the full model. By model simulations and real data applications, we demonstrate the feasibility of our fitting strategies and achieve convincing results. Using clinically affordable diffusion acquisition paradigms (encoding numbers: 21, 2*15, 2*21) and b values (b =500–1500s/mm2), this methodology can place the TTM parameters involved in crossing fibers on a more empirical basis than fitting procedures with technical assumptions. [Copyright &y& Elsevier]