Resolution Diffusion Tensor Imaging Research Articles

Normobaric hyperoximia increases hypoxia‐induced cerebral injury: DTI study in rats

Perinatal hypoxia affects normal neurological development and can lead to motor, behavioral and cognitive deficits. A common acute treatment for perinatal hypoxia is oxygen resuscitation (hyperoximia), a controversial treatment. Magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI), was performed in a P7 rat model of perinatal hypoxia to determine the effect of hyperoximia. These studies were performed on two groups of animals: 1) animals which were subjected to ischemia followed by hypoxia (HI), and 2) HI followed by hyperoximic treatment (HHI). Lesion volumes on high resolution MRI and DTI derived measures, fractional anisotropy (FA), mean diffusivity (MD), and axial and radial diffusivities (lambda(l) and lambda(t), respectively) were measured in vivo one day, one week, and three weeks after injury. Most significant differences in the MRI and DTI measures were found at three weeks after injury. Specifically, three weeks after HHI injury resulted in significantly larger hyperintense lesion volumes (95.26 +/- 50.42 mm(3)) compared to HI (22.25 +/- 17.62 mm(3)). The radial diffusivity lambda(t) of the genu of corpus callosum was significantly larger in HHI (681 +/- 330 x 10(-6) mm(2)/sec) than in HI (486 +/- 96 x 10(-6) mm(2)/sec). Over all, most significant differences in all the DTI metrics (FA, MD, lambda(t), lambda(l)) at all time points were found in the corpus callosum. Our results suggest that treatment of perinatal hypoxia with normobaric oxygen does not ameliorate, but exacerbates damage.

Combinatorial fiber-tracking of the human brain

This paper presents a novel fiber-tracking algorithm, termed combinatorial tracking, which uses stochastic process modeling and global optimization algorithm for tractography. Combinatorial tracking is a probabilistic tracking algorithm that transforms the brain's white matter into a grid in which each voxel has 26 weighted connections with adjacent voxels. We model the random walk on this graph using a Markov Chain model and suggest two approaches for fiber reconstruction. In the first approach, we find the most probable paths between two voxels with prior connectivity knowledge using a shortest path algorithm. In the second approach, the all-pairs mean first passage time (MFPT) matrix M (or hitting time as referred to in the Spectral Graph theory literature) is calculated analytically. We suggest that M can be interpreted as a global connectivity matrix and use it for fiber reconstruction. We also introduce a simulation framework that can be used to calculate specific elements of the matrix M, and show how it can be employed to select the target of a fiber in a high resolution diffusion tensor imaging (DTI) dataset. Because any source and any target voxel can be connected, combinatorial tracking permits true connectivity analysis, overcoming the limitations of conventional tracking, especially stopping criteria (e.g. low FA). We applied combinatorial tracking to a standard DTI dataset and demonstrated the reconstruction of the cortico-thalamic pathway, the pyramidal decussation, and the medial cerebellar peduncle fibers. While the DTI ellipsoid served as input for the algorithms, any diffusion imaging based orientation density function (ODF) can be used. This framework can potentially turn diffusion imaging tractography into a true connectivity measure.

High resolution diffusion-weighted imaging in fixed human brain using diffusion-weighted steady state free precession

High resolution diffusion tensor imaging and tractography of ex vivo brain specimens has the potential to reveal detailed fibre architecture not visible on in vivo images. Previous ex vivo diffusion imaging experiments have focused on animal brains or small sections of human tissue since the unfavourable properties of fixed tissue (including short T2 and low diffusion rates) demand the use of very powerful gradient coils that are too small to accommodate a whole, human brain. This study proposes the use of diffusion-weighted steady-state free precession (DW-SSFP) as a method of extending the benefits of ex vivo DTI and tractography to whole, human, fixed brains on a clinical 3 T scanner. DW-SSFP is a highly efficient pulse sequence; however, its complicated signal dependence precludes the use of standard diffusion tensor analysis and tractography. In this study, a method is presented for modelling anisotropy in the context of DW-SSFP. Markov Chain Monte Carlo sampling is used to estimate the posterior distributions of model parameters and it is shown that it is possible to estimate a tight distribution on the principal axis of diffusion at each voxel using DW-SSFP. Voxel-wise estimates are used to perform tractography in a whole, fixed human brain. A direct comparison between 3D diffusion-weighted spin echo EPI and 3D DW-SSFP-EPI reveals that the orientation of the principal diffusion axis can be inferred on with a higher degree of certainty using a 3D DW-SSFP-EPI even with a 68% shorter acquisition time.

High-resolution diffusion tensor imaging in the substantia nigra of de novo Parkinson disease

In the midbrain of patients with Parkinson disease (PD), there is a selective loss of dopaminergic neurons in the ventrolateral and caudal substantia nigra (SN). In a mouse model of PD, investigators have administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and found that measures derived using diffusion tensor imaging (DTI) were correlated with the number of dopamine neurons lost following intoxication. Twenty-eight subjects (14 with early stage, untreated PD and 14 age- and gender-matched controls) were studied with a high-resolution DTI protocol at 3 Tesla using an eight-channel phase array coil and parallel imaging to study specific segments of degeneration in the SN. Regions of interest were drawn in the rostral, middle, and caudal SN by two blinded and independent raters. Fractional anisotropy (FA) was reduced in the SN of subjects with PD compared with controls (p < 0.001). Post hoc analysis identified that reduced FA for patients with PD was greater in the caudal compared with the rostral region of interest (p < 0.00001). A receiver operator characteristic analysis in the caudal SN revealed that sensitivity and specificity were 100% for distinguishing patients with PD from healthy subjects. Findings were consistent across both raters. These findings provide evidence that high resolution diffusion tensor imaging in the substantia nigra distinguishes early stage, de novo patients with Parkinson disease (PD) from healthy individuals on a patient by patient basis and has the potential to serve as a noninvasive early biomarker for PD.

Mapping the human brain white matter tracts relative to cortical and deep gray matter using diffusion tensor imaging at high spatial resolution

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.

Regional networks underlying interhemispheric connectivity: An EEG and DTI study in healthy ageing and amnestic mild cognitive impairment

Interhemispheric coherence derived from electroencephalogram (EEG) recordings is a measure of functional interhemispheric connectivity. Diffusion tensor imaging (DTI) determines the integrity of subcortical fiber tracts. We studied the pattern of subcortical fiber tracts underlying interhemispheric coherence and its alteration in 16 subjects with amnestic mild cognitive impairment (MCI), an at risk syndrome for Alzheimer's disease, and 20 cognitively healthy elderly control subjects using resting state EEG and high resolution DTI at 3 T. We used a multivariate network approach based on principal component analysis to determine effects of coherence on the regional pattern of diffusivity. Temporo-parietal coherence in the alpha band was significantly correlated with diffusivity in predominantly posterior white matter tracts including posterior corpus callosum, parietal, temporal and occipital lobe white matter, thalamus, midbrain, pons, and cerebellum, both in MCI subjects and controls (P < 0.05). In MCI subjects, frontal coherence in the alpha band was significantly correlated with a predominately frontal pattern of diffusivity including fiber tracts of the anterior corpus callosum, frontal lobe white matter, thalamus, pons, and cerebellum (P < 0.05). The study provides a methodology to access specific networks of subcortical fiber tracts subserving the maintenance of interhemispheric resting state coherence in the human brain.

Sensitivity of diffusion weighted steady state free precession to anisotropic diffusion

Diffusion-weighted steady-state free precession (DW-SSFP) accumulates signal from multiple echoes over several TRs yielding a strong sensitivity to diffusion with short gradient durations and imaging times. Although the DW-SSFP signal is well characterized for isotropic, Gaussian diffusion, it is unclear how the DW-SSFP signal propagates in inhomogeneous media such as brain tissue. This article presents a more general analytical expression for the DW-SSFP signal which accommodates Gaussian and non-Gaussian spin displacement probability density functions. This new framework for calculating the DW-SSFP signal is used to investigate signal behavior for a single fiber, crossing fibers, and reflective barriers. DW-SSFP measurements in the corpus callosum of a fixed brain are shown to be in good agreement with theoretical predictions. Further measurements in fixed brain tissue also demonstrate that 3D DW-SSFP out-performs 3D diffusion weighted spin echo in both SNR and CNR efficiency providing a compelling example of its potential to be used for high resolution diffusion tensor imaging.

Anatomía de la sustancia blanca mediante tractografía por tensor de difusión

Tractography of cerebral white matter fibers based on diffusion tensor imaging (DTI) is a recent magnetic resonance technique that enables the visualization of the anatomy and integrity of white matter tracts. This article aims to provide two- and three-dimensional representations of the main white matter tracts in the brain from high spatial resolution DTI data and to explain the physical basis of the technique, its main clinical applications, and how we use it. We provide examples of the use of DTI in the study of the corpus callosum, the anterior white commissure, the corticospinal tract, the limbic system, the long association fibers, the cerebellar peduncles, and the optic tract.

Anatomical parcellation of the brainstem and cerebellar white matter: a preliminary probabilistic tractography study at 3 T

The aims of this study were: (1) to test whether higher spatial resolution diffusion tensor images and a higher field strength (3 T) enable a more accurate delineation of the anatomical tract within the brainstem, and, in particular, (2) to try to distinguish the different components of the corticopontocerebellar paths in terms of their cortical origins. The main tracts of the brainstem of four volunteers were studied at 3 T using a probabilistic diffusion tensor imaging (DTI) axonal tracking. The resulting tractograms enabled anatomical well-delineated structures to be identified on the diffusion tensor coloured images. We tracked corticopontine, corticospinal, central tegmental, inferior and superior cerebellopeduncular, transverse, medial lemniscal and, possibly, longitudinal medial fibres. Moreover, DTI tracking allowed a broad delineation of the corticopontocerebellar paths. Diffusion tensor coloured images allow a rapid and reliable access to the white matter broad parcellation of the brainstem and of the cerebellum, which can be completed by fibre tracking. However, a more accurate and exhaustive depiction of the anatomical connectivity within the brainstem requires the application of more sophisticated techniques and tractography algorithms, such as diffusion spectrum imaging.

High resolution diffusion tensor imaging of axonal damage in focal inflammatory and demyelinating lesions in rat spinal cord

Inflammation, demyelination, gliosis and axonal degeneration are pathological hallmarks of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis. Axonal damage is thought to contribute to irreversible damage and functional impairment, but is difficult to quantify. Conventional MRI has been used to assess the inflammatory and demyelinating aspects of MS lesions, but more sensitive and specific methods are needed to identify axonal damage to monitor disease progression and to determine efficacy of putative neuroprotective agents. We used high resolution diffusion tensor imaging (DTI) and fibre tracking to examine the spinal cord in rats with focal dorsal column inflammatory or demyelinating lesions to determine whether DTI measures can be used to detect pathology at the site of the focal lesion and to measure axonal damage in tracts distal to the focal lesion. Distant from the focal lesion, total axon counts, degenerating axon counts and SMI-31 staining, but not Luxol fast blue staining, were significantly correlated with fractional anisotropy, axial diffusivity and radial diffusivity, all of which are derived from the DTI data. These data suggest that high resolution DTI may be a more sensitive method than conventional imaging for detecting axonal damage at sites distant from inflammation.

Optimal estimation of the diffusion coefficient from non-averaged and averaged noisy magnitude data

The magnitude operation changes the signal distribution in MRI images from Gaussian to Rician. This introduces a bias that must be taken into account when estimating the apparent diffusion coefficient. Several estimators are known in the literature. In the present paper, two novel schemes are proposed. Both are based on simple least squares fitting of the measured signal, either to the median (MD) or to the maximum probability (MP) value of the Probability Density Function (PDF). Fitting to the mean (MN) or a high signal-to-noise ratio approximation to the mean (HS) is also possible. Special attention is paid to the case of averaged magnitude images. The PDF, which cannot be expressed in closed form, is analyzed numerically. A scheme for performing maximum likelihood (ML) estimation from averaged magnitude images is proposed. The performance of several estimators is evaluated by Monte Carlo (MC) simulations. We focus on typical clinical situations, where the number of acquisitions is limited. For non-averaged data the optimal choice is found to be MP or HS, whereas uncorrected schemes and the power image (PI) method should be avoided. For averaged data MD and ML perform equally well, whereas uncorrected schemes and HS are inadequate. MD provides easier implementation and higher computational efficiency than ML. Unbiased estimation of the diffusion coefficient allows high resolution diffusion tensor imaging (DTI) and may therefore help solving the problem of crossing fibers encountered in white matter tractography.

The effects of brain tissue decomposition on diffusion tensor imaging and tractography

There have been numerous high resolution diffusion tensor imaging studies in fixed animal brains, but relatively few studies in human brains. While animal tissues are generally fixed pre-mortem or directly postmortem, this is not possible for human tissue, therefore there is always some delay between death and tissue fixation. The elapsed time between death and tissue fixation, the postmortem interval (PMI), will most likely adversely affect the tissue's diffusion properties. We studied the effects of PMI on the diffusion properties of rodent brain. Eight mice were euthanized and the brains (kept in the skull) were placed in formalin at PMIs of 0, 1, 4 and 14 days. Post fixation they were placed in a solution of GdDTPA and phosphate buffered saline. Brains were scanned with a 3D EPI DTI sequence at 4.7T. DTI data were processed to generate apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps. DTI tractography was also performed. The temporal changes in regional ADC and FA values were analyzed statistically using a one-way ANOVA, followed by individual Student's T-tests. Regional FA and ADC of gray and white matter decreased significantly with time (p<0.05). DTI tractography showed a decrease in the number and coherence of reconstructed fiber pathways between PMIs 0 and 14. Elapsed time between death and tissue fixation has a major effect upon the brain's diffusion properties and should be born in mind when interpreting fixed brain DTI.

An approach to high resolution diffusion tensor imaging in fixed primate brain

High resolution ex vivo diffusion tensor imaging (DTI) studies of neural tissues can improve our understanding of brain structure. In these studies we can modify the tissue relaxation properties of the fixed tissues to better suite the scanner hardware. We investigated the use of Gd-DTPA contrast agent to provide the optimum signal-to-noise (SNR) ratio in 3D DTI scans of formalin fixed nonhuman primate brains at 4.7 T. Relaxivity measurements in gray and white matter allowed us to optimize the Gd concentration for soaking the brains, resulting in a 2 fold improvement in SNR for the 3D scans. FA changed little with Gd concentrations up to 10 mM although ADC was reduced at 5 and 10 mM. Comparison of in vivo, fresh ex vivo and fixed brains showed no significant FA changes but reductions in ADC of about 50% in fresh ex vivo, and 64% and 80% in fixed gray and white matter respectively. Studies of the temperature dependence of diffusion in these tissues suggested that a 30° increase in sample temperature may yield an improvement of up to 55% in SNR-efficiency for a given diffusion weighting. Our Gd soaking regimen appeared to have no detrimental effect on standard histology of the fixed brain sections. Our methods yield both high SNR and spatial resolution DTI data in fixed primate brains, allowing us to perform high resolution tractography which will facilitate the process of ‘validation’ of DTI fiber tracts against traditional measures of brain fiber architecture.

Mapping postnatal mouse brain development with diffusion tensor microimaging

While mouse brain development has been extensively studied using histology, quantitative characterization of morphological changes is still a challenging task. This paper presents how developing brain structures can be quantitatively characterized with magnetic resonance diffusion tensor microimaging coupled with techniques of computational anatomy. High resolution diffusion tensor images of ex vivo postnatal mouse brains provide excellent contrasts to reveal the evolutions of mouse forebrain structures. Using anatomical landmarks defined on diffusion tensor images, tissue level growth patterns of mouse brains were quantified. The results demonstrate the use of these techniques to three-dimensionally and quantitatively characterize brain growth.

Diffusion tensor imaging for the assessment of upper motor neuron integrity in ALS

High angular resolution diffusion tensor imaging (HARD) is an MRI technique that exploits the mobility of water molecules to yield maps of structural order and directionality of white matter tracts with greater precision than six-direction diffusion tensor imaging (DTI) schemes. To assess whether HARD is more sensitive than conventional MRI or neurologic assessment in detecting the upper motor neuron (UMN) pathology of patients with ALS. Twenty-five patients with definite UMN clinical signs and 23 healthy volunteers underwent conventional MRI. HARD datasets were collected from a subset of these participants plus four patients with isolated lower motor neuron (LMN) signs. ALS symptom severity was assessed by a neurologist, the conventional MR images were reviewed by neuroradiologists, and the DTI maps were subject to quantitative region of interest analysis. Motor cortex hypointensity on T2-weighted images and corona radiata hyperintensity on proton density-weighted images distinguished patients with UMN involvement from volunteers with 100% specificity, but only 20% sensitivity. Fractional anisotropy (FA) was reduced in the posterior limb of the internal capsule in patients with UMN involvement compared to volunteers. A FA threshold value with a sensitivity of 95% to detect patients with ALS (including those with isolated LMN signs) had a specificity of 71%. High angular resolution diffusion tensor imaging may be more sensitive than conventional MRI or neurologic assessment to the upper motor neuron (UMN) pathology of ALS, but it lacks the specificity required of a diagnostic marker. Instead, it is potentially useful as a quantitative tool for monitoring the progression of UMN pathology.

Isotropic resolution diffusion tensor imaging with whole brain acquisition in a clinically acceptable time.

Our objective was to develop a diffusion tensor MR imaging pulse sequence that allows whole brain coverage with isotropic resolution within a clinically acceptable time. A single-shot, cardiac-gated MR pulse sequence, optimized for measuring the diffusion tensor in human brain, was developed to provide whole-brain coverage with isotropic (2.5 x 2.5 x 2.5 mm) spatial resolution, within a total imaging time of approximately 15 min. The diffusion tensor was computed for each voxel in the whole volume and the data processed for visualization in three orthogonal planes. Anisotropy data were further visualized using a maximum-intensity projection algorithm. Finally, reconstruction of fiber-tract trajectories i.e., "tractography" was performed. Images obtained with this pulse sequence provide clear delineation of individual white matter tracts, from the most superior cortical regions down to the cerebellum and brain stem. Because the data are acquired with isotropic resolution, they can be reformatted in any plane and the sequence can therefore be used, in general, for macroscopic neurological or psychiatric neuroimaging investigations. The 3D visualization afforded by maximum intensity projection imaging and tractography provided easy visualization of individual white matter fasciculi, which may be important sites of neuropathological degeneration or abnormal brain development. This study has shown that it is possible to obtain robust, high quality diffusion tensor MR data at 1.5 Tesla with isotropic resolution (2.5 x 2.5 x 2.5 mm) from the whole brain within a sufficiently short imaging time that it may be incorporated into clinical imaging protocols.

High spatial resolution diffusion tensor imaging without cardiac gating: Comparison between Segmented EPI and Half Fourier Acquisition

High spatial resolution diffusion tensor imaging without cardiac gating: Comparison between Segmented EPI and Half Fourier Acquisition