Novel diffusion tensor imaging methodology to detect and quantify injured regions and affected brain pathways in traumatic brain injury

Purpose

To develop and apply diffusion tensor imaging (DTI)-based normalization methodology for the detection and quantification of sites of traumatic brain injury (TBI) and the impact of injury along specific brain pathways in (a) individual TBI subjects and (b) a TBI group.

Materials and Methods

Normalized DTI tractography was conducted in the native space of 12 TBI and 10 age-matched control subjects using the same number of seeds in each subject, distributed at anatomically equivalent locations. Whole-brain tracts from the control group were mapped onto the head of each TBI subject. Differences in the fractional anisotropy (FA) maps between each TBI subject and the control group were computed in a common space using a t test, transformed back to the individual TBI subject's head space, and thresholded to form regions of interest (ROIs) that were used to sort tracts from the control group and the individual TBI subject. Tract counts for a given ROI in each TBI subject were compared to group mean for the same ROI to quantify the impact of injury along affected pathways. The same procedure was used to compare the TBI group to the control group in a common space.

Results

Sites of injury within individual TBI subjects and affected pathways included hippocampal/fornix, inferior fronto-occipital, inferior longitudinal fasciculus, corpus callosum (genu and splenium), cortico-spinal tracts and the uncinate fasciculus. Most of these regions were also detected in the group study.

Conclusions

The DTI normalization methodology presented here enables automatic delineation of ROIs within the heads of individual subjects (or in a group). These ROIs not only localize and quantify the extent of injury, but also quantify the impact of injury on affected pathways in an individual or in a group of TBI subjects.     

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.     

Complimentary aspects of diffusion imaging and fMRI: II. Elucidating contributions to the fMRI signal with diffusion sensitization

Tissue water molecules reside in different biophysical compartments. For example, water molecules in the vasculature reside for variable periods of time within arteries, arterioles, capillaries, venuoles and veins, and may be within blood cells or blood plasma. Water molecules outside of the vasculature, in the extravascular space, reside, for a time, either within cells or within the interstitial space between cells. Within these different compartments, different types of microscopic motion that water molecules may experience have been identified and discussed. These range from Brownian diffusion to more coherent flow over the time scales relevant to functional magnetic resonance imaging (fMRI) experiments, on the order of several 10s of milliseconds. How these different types of motion are reflected in magnetic resonance imaging (MRI) methods developed for "diffusion" imaging studies has been an ongoing and active area of research. Here we briefly review the ideas that have developed regarding these motions within the context of modern "diffusion" imaging techniques and, in particular, how they have been accessed in attempts to further our understanding of the various contributions to the fMRI signal changes sought in studies of human brain activation.     

Intermolecular double quantum coherences (iDQc) and diffusion-weighted imaging (DWI) imaging of the human brain at 1.5 T

To study the sensitivity of intermolecular double quantum coherences (iDQc) imaging contrast to brain microstructure and brain anisotropy, we investigated the iDQC contrast between differently structured areas of the brain according to the strength and the direction of the applied correlation gradient. Thus diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) maps have been obtained. This procedure, which consists of analyzing both iDQc and DWI images at different gradient strength and gradient direction, could be a promising tool for clinical brain investigations performed with higher than 1.5 T magnetic fields.     

Central neurocytoma: proton MR spectroscopy and diffusion weighted MR imaging findings

Purpose

To present proton magnetic resonance spectroscopy and diffusion-weighted imaging (DWI) findings of central neurocytoma (CN).

Methods and Materials

Imaging findings of seven patients with the histopathological diagnosis of CN (five male and two female; age range, 21–28 years of age) were evaluated retrospectively. In addition to conventional magnetic resonance imaging features, we also assessed the metabolite ratios and tumor normalized apparent diffusion coefficient (NADC), which was calculated by dividing the tumor apparent diffusion coefficient (ADC) values by normal ADC. Approval from our institutional review board was obtained for this review.

Results

The tumor choline/creatine ratios were 5.17±2.38, while N-acetyl aspartate/choline and N-acetyl aspartate/creatine ratios were 0.33±0.15 and 1.84±1.38, respectively. On DWI, tumors had heterogeneous hyperintense appearances when compared with the contralateral parietal lobe white matter and tumor NADC values were 0.63±0.05.

Conclusion

Significantly increased choline/creatine and decreased N-acetyl aspartate/choline ratios with lower NADC values in CN resemble high-grade gliomas and complicate the diagnosis. Familarity its physiologic features would help to presurgical diagnosis of ventricular and exraventricular CNs.     

On the effects of dephasing due to local gradients in diffusion tensor imaging experiments: relevance for diffusion tensor imaging fiber phantoms

The effect of susceptibility differences between fluid and fibers on the properties of DTI fiber phantoms was investigated. Thereto, machine-made, easily producible and inexpensive DTI fiber phantoms were constructed by winding polyamide fibers of 15 microm diameter around a circular acrylic glass spindle. The achieved fractional anisotropy was 0.78+/-0.02. It is shown by phantom measurements and Monte Carlo simulations that the transversal relaxation time T(2) strongly depends on the angle between the fibers and the B(0) field if the susceptibilities of the fibers and fluid are not identical. In the phantoms, the measured T(2) time at 3 T decreased by 60% for fibers running perpendicular to B(0). Monte Carlo simulations confirmed this result and revealed that the exact relaxation time depends strongly on the exact packing of the fibers. In the phantoms, the measured diffusion was independent of fiber orientation. Monte Carlo simulations revealed that the measured diffusion strongly depends on the exact fiber packing and that field strength and -orientation dependencies of measured diffusion may be minimal for hexagonal packing while the diffusion can be underestimated by more than 50% for cubic packing at 3 T. To overcome these effects, the susceptibilities of fibers and fluid were matched using an aqueous sodium chloride solution (83 g NaCl per kilogram of water). This enables an orientation independent and reliable use of DTI phantoms for evaluation purposes.     

Voxel- and atlas-based analysis of diffusion tensor imaging may reveal focal axonal injuries in mild traumatic brain injury -- comparison with diffuse axonal injury

Background

The diagnosis and management of mild traumatic brain injury (MTBI) continue to be subjects of debate, with varying opinions regarding the extent to which tissue-based impairments versus the impacts of other stressors cause ongoing disability. Detecting areas of the brain with abnormalities that can explain symptoms and behavior in patients with MTBI is important in order to confirm the diagnosis of MTBI.

Methods

In this study, we calculated diffusion maps from results of diffusion tensor imaging (DTI) performed in an apparently healthy control group. We then compared these maps with those of patients with MTBI (MTBI group) or diffuse axonal injury (DAI group). All diffusion maps were normalized to the International Consortium for Brain Mapping atlas for atlas-based analysis and were segmented and normalized by the Diffeomorphic Anatomical Registration Through Exponentiated Lie tool in SPM8 to reduce misregistration.

Results

All diffusion measures in the DAI group were lower than in the control group. There were significant differences in the body and splenium of the corpus callosum, fornix and right cerebral peduncle in the DAI group compared with the control group (P<.001). The MTBI group had higher axial diffusivity than the control group in the right corticospinal tract, left medial lemniscus, left inferior cerebellar peduncle, bilateral anterior limb of the internal capsule, right anterior corona radiata, bilateral cingulum (cingulate gyrus) and left superior frontooccipital fasciculus (P<.05).

Conclusions

Voxel- and atlas-based analysis of DTI might suggest that patients with MTBI have focal axonal injury and that the pathophysiology is significantly different from that of DAI. These findings will help in the diagnosis of patients with MTBI.     

Reproducibility and biases in high field brain diffusion MRI: An evaluation of acquisition and analysis variables

Diffusion tensor imaging (DTI) of in-vivo human brain provides insights into white matter anatomical connectivity, but little is known about measurement difference biases and reliability of data obtained with last generation high field scanners (> 3 T) as function of MRI acquisition and analyses variables. Here we assess the impact of acquisition (voxel size: 1.8 × 1.8 × 1.8, 2 × 2 × 2 and 2.5 × 2.5 × 2.5 mm³, b-value: 700, 1000 and 1300 s/mm²) and analysis variables (within-session averaging and co-registration methods) on biases and test-retest reproducibility of some common tensor derived quantities like fractional anisotropy (FA), mean diffusivity (MD), axial and radial diffusivity in a group of healthy subjects at 4 T in three regions: arcuate fasciculus, corpus callosum and cingulum. Averaging effects are also evaluated on a full-brain voxel based approach. The main results are: i) group FA and MD reproducibility errors across scan sessions are on average double of those found in within-session repetitions (≈ 1.3 %), regardless of acquisition protocol and region; ii) within-session averaging of two DTI acquisitions does not improve reproducibility of any of the quantities across sessions at the group level, regardless of acquisition protocol; iii) increasing voxel size biased MD, axial and radial diffusivities to higher values and FA to lower values; iv) increasing b-value biased all quantities to lower values, axial diffusivity showing the strongest effects; v) the two co-registration methods evaluated gave similar bias and reproducibility results. Altogether these results show that reproducibility of FA and MD is comparable to that found at lower fields, not significantly dependent on pre-processing and acquisition protocol manipulations, but that the specific choice of acquisition parameters can significantly bias the group measures of FA, MD, axial and radial diffusivities.     

Diffusional kurtosis imaging of cingulate fibers in Parkinson disease: Comparison with conventional diffusion tensor imaging

Objective

The pathological changes in Parkinson disease begin in the brainstem; reach the limbic system and ultimately spread to the cerebral cortex. In Parkinson disease (PD) patients, we evaluated the alteration of cingulate fibers, which comprise part of the limbic system, by using diffusional kurtosis imaging (DKI).

Methods

Seventeen patients with PD and 15 age-matched healthy controls underwent DKI with a 3-T MR imager. Diffusion tensor tractography images of the anterior and posterior cingulum were generated. The mean kurtosis (MK) and conventional diffusion tensor parameters measured along the images in the anterior and posterior cingulum were compared between the groups. Receiver operating characteristic (ROC) analysis was also performed to compare the diagnostic abilities of the MK and conventional diffusion tensor parameters.

Results

The MK and fractional anisotropy (FA) in the anterior cingulum were significantly lower in PD patients than in healthy controls. The area under the ROC curve was 0.912 for MK and 0.747 for FA in the anterior cingulum. MK in the anterior cingulum had the best diagnostic performance (mean cutoff, 0.967; sensitivity, 0.87; specificity, 0.94).

Conclusions

DKI can detect alterations of the anterior cingulum in PD patients more sensitively than can conventional diffusion tensor imaging. Use of DKI can be expected to improve the ability to diagnose PD.     

NMR imaging in human pregnancy: A preliminary study

In an effort to demonstrate the potential of nuclear magnetic resonance imaging (NMR) in the management of pregnancy, 15 patients in the first trimester and one in the third trimester of pregnancy have been investigated in the Aberdeen University NMR imager. Simple measurements of biparietal diameter and crown-rump length were made from both the NMR images and the ultrasound images on the same day, with good correlation between the two. The NMR data was displayed as inversion recovery, calculated T₁, proton density and S₁–S₂ images. The proton density and S₁–S₂ images were found to be the most useful for the demonstration of the fetus and for discriminating between placenta and uterus. The calculated T₁ data provided accurate quantification of the proton-spin lattice relaxation times of the different tissues, indicating that this measurement may be of use in the study of fetal brain development and placental function. The inversion recovery images showed poor tissue discrimination and were found to be of limited value. The unique information available using NMR and the non-invasive nature of the technique indicated that it should provide a useful method for the investigation of both fetal development and placental function in addition to making basic measurements of fetal size.     

Sexual dimorphism in the human brain: evidence from neuroimaging

In recent years, more and more emphasis has been placed on the investigation of sex differences in the human brain. Noninvasive neuroimaging techniques represent an essential tool in the effort to better understand the effects of sex on both brain structure and function. In this review, we provide a comprehensive summary of the findings that were collected in human neuroimaging studies in vivo thus far: we explore sexual dimorphism in the human brain at the level of (1) brain structure, in both gray and white matter, observed by voxel-based morphometry (VBM) and diffusion tensor imaging (DTI), respectively; (2) baseline neural activity, studied using resting-state functional magnetic resonance imaging (rs-fMRI) and positron emission tomography (PET); (3) neurochemistry, visualized by means of neuroreceptor ligand PET; and (4) task-related neural activation, investigated using fMRI. Functional MRI findings from the literature are complemented by our own meta-analysis of fMRI studies on sex-specific differences in human emotional processing. Specifically, we used activation likelihood estimation (ALE) to provide a quantitative approach to mapping the consistency of neural networks involved in emotional processing across studies. The presented evidence for sex-specific differences in neural structure and function highlights the importance of modeling sex as a contributing factor in the analysis of brain-related data.     

Repeatability of echo-planar-based diffusion measurements of the human prostate at 3 T

Echo-planar-based diffusion-weighted imaging (DWI) of the prostate is increasingly being suggested as a viable technique, complementing information derived from conventional magnetic resonance imaging methods for use in tissue discrimination. DWI has also been suggested as a potentially useful tool in the assessment of tumor response to treatment. In this study, the repeatability of apparent diffusion coefficient (ADC) values obtained from both DWI and diffusion tensor imaging (DTI) has been assessed as a precursor to determining the magnitude of treatment-induced changes required for reliable detection. The repeatability values of DWI and DTI were found to be similar, with ADC values repeatable to within 35% or less over a short time period of a few minutes and a longer time period of a month. Fractional anisotropy measurements were found to be less repeatable (between 26% and 71%), and any changes duly recorded in longitudinal studies must therefore be treated with a degree of caution.     

Development and initial evaluation of 7-T q-ball imaging of the human brain

Diffusion tensor imaging (DTI) noninvasively depicts white matter connectivity in regions where the Gaussian model of diffusion is valid but yields inaccurate results in those where diffusion has a more complex distribution, such as fiber crossings. q-ball imaging (QBI) overcomes this limitation of DTI by more fully characterizing the angular dependence of intravoxel diffusion with larger numbers of diffusion-encoding directional measurements at higher diffusion-weighting factors (b values). However, the former technique results in longer acquisition times and the latter technique results in a lower signal-to-noise ratio (SNR). In this project, we developed specialized 7-T acquisition methods utilizing novel radiofrequency pulses, eight-channel parallel imaging EPI and high-order shimming with a phase-sensitive multichannel B0 field map reconstruction. These methods were applied in initial healthy adult volunteer studies, which demonstrated the feasibility of performing 7-T QBI. Preliminary comparisons of 3 T with 7 T within supratentorial crossing white matter tracts documented a 79.5% SNR increase for b=3000 s/mm2 (P=.0001) and a 38.6% SNR increase for b=6000 s/mm2 (P=.015). With spherical harmonic reconstruction of the q-ball orientation distribution function at b=3000 s/mm2, 7-T QBI allowed for accurate visualization of crossing fiber tracts with fewer diffusion-encoding acquisitions as compared with 3-T QBI. The improvement of 7-T QBI at b factors as high as 6000 s/mm2 resulted in better angular resolution as compared with 3-T QBI for depicting fibers crossing at shallow angles. Although the increased susceptibility effects at 7 T caused problematic distortions near brain-air interfaces at the skull base and posterior fossa, these initial 7-T QBI studies demonstrated excellent quality in much of the supratentorial brain, with significant improvements as compared with 3-T acquisitions in the same individuals.     

Keyhole and zero-padding approaches for reduced-encoding diffusion tensor imaging of the mouse brains

Keyhole diffusion tensor imaging (keyhole DTI) was previously proposed in cardiac imaging to reconstruct DTI maps from the reduced phase-encoding images. To evaluate the feasibility of keyhole DTI in brain imaging, keyhole and zero-padding DTI algorithms were employed on in vivo mouse brain. The reduced phase-encoding portion, also termed as the sharing rate, was varied from 50% to 90% of the full k-space. Our data showed that zero-padding DTI resulted in decreased fractional anisotropy (FA) and decreased mean apparent diffusion coefficient (mean ADC) in white matter (WM) regions. Keyhole DTI showed a better edge preservation on mean ADC maps but not on FA maps as compared to the zero-padding DTI. When increasing the sharing rate in keyhole approach, an underestimation of FA and an over- or underestimation of mean ADC were measured in WM depending on the selected reference image. The inconsistency of keyhole DTI may add a challenge for the wide use of this modality. However, with a carefully selected directive diffusion-weighted image to serve as the reference image in the keyhole approach, this study demonstrated that one may obtain DTI indices of reduced-encoding images with high consistency to those derived with full k-space DTI.     

Assessing functional connectivity in the human brain by fMRI

Functional magnetic resonance imaging (fMRI) is widely used to detect and delineate regions of the brain that change their level of activation in response to specific stimuli and tasks. Simple activation maps depict only the average level of engagement of different regions within distributed systems. FMRI potentially can reveal additional information about the degree to which components of large-scale neural systems are functionally coupled together to achieve specific tasks. In order to better understand how brain regions contribute to functionally connected circuits, it is necessary to record activation maps either as a function of different conditions, at different times or in different subjects. Data obtained under different conditions may then be analyzed by a variety of techniques to infer correlations and couplings between nodes in networks. Several multivariate statistical methods have been adapted and applied to analyze variations within such data. An approach of particular interest that is suited to studies of connectivity within single subjects makes use of acquisitions of runs of MRI images obtained while the brain is in a so-called steady state, either at rest (i.e., without any specific stimulus or task) or in a condition of continuous activation. Interregional correlations between fluctuations of MRI signal potentially reveal functional connectivity. Recent studies have established that interregional correlations between different components of circuits in each of the visual, language, motor and working memory systems can be detected in the resting state. Correlations at baseline are changed during the performance of a continuous task. In this review, various methods available for assessing connectivity are described and evaluated.     

Effect of B-value in revealing postinfarct myocardial microstructural remodeling using MR diffusion tensor imaging

Nonmonoexponential diffusion behavior has been previously reported to exist in some biological tissues, making quantification of diffusion tensor imaging (DTI) indices dependent on diffusion sensitivity of b-value. This study aims to investigate the effect of b-value in revealing postinfarct myocardial microstructural remodeling in ex vivo hearts. DTI scans were performed on heart samples 1, 3, 5, and 7 days after infarction induction as well as intact controls with b-values of 500 to 2500 s/mm². DTI indices, including fractional anisotropy (FA), and mean and directional diffusivities, were measured in infarct, adjacent and remote regions with zero and each non-zero b-values respectively using conventional DTI analysis. Experimental results showed that these DTI indices decreased gradually with b-values in all regions and groups. Optimal b-values were found to vary with targeted DTI indices, and could strengthen DTI ability in revealing myocardium degradation with using conventional DTI approach. Specifically, FA showed the most sensitive detection of fiber integrity degradation at moderate b-values (≈ 1500 to 2000 s/mm²), and the greatest ability of mean and directional diffusivities in monitoring diffusivity alteration occurred at relatively small b-values (≤ 1500 s/mm²) during the necrotic and fibrotic phases. These findings may provide useful information for DTI protocol parameter optimization in assessing heart microstructures at other pathological or in vivo states in the future.     

Validation of the anisotropy index ellipsoidal area ratio in diffusion tensor imaging

A new diffusion anisotropy index, ellipsoidal area ratio (EAR), was described recently and proved to be less noise-sensitive than fractional anisotropy (FA) by theory and simulation. Here we show that EAR has higher signal-to-noise ratios than FA in average diffusion tensor imaging data from 40 normal subjects. EAR was also more sensitive than FA in detecting white matter abnormalities in a patient with widespread diffuse axonal injury. Monte Carlo simulation showed that EAR's mean values are more biased by noise than FA when anisotropy is small, both for single fiber tracts and when fiber tracts cross. However, the improved signal-to-noise ratio of EAR relative to FA suggests that EAR may be a superior measure of anisotropy both in quantifying both deep white matter with relatively uniform fiber tracts and pericortical white matter structure with relatively low anisotropy and fiber crossings.     

Optimal real-time estimation in diffusion tensor imaging

Diffusion tensor imaging (DTI) constitutes the most used paradigm among the diffusion-weighted magnetic resonance imaging (DW-MRI) techniques due to its simplicity and application potential. Recently, real-time estimation in DW-MRI has deserved special attention, with several proposals aiming at the estimation of meaningful diffusion parameters during the repetition time of the acquisition sequence. Specifically focusing on DTI, the underlying model of the noise present in the acquired data is not taken into account, leading to a suboptimal estimation of the diffusion tensor. In this paper, we propose an optimal real-time estimation framework for DTI reconstruction in single-coil acquisitions. By including an online estimation of the time-changing noise variance associated to the acquisition process, the proposed method achieves the sequential best linear unbiased estimator. Results on both synthetic and real data show that our method outperforms those so far proposed, reaching the best performance of the existing proposals by processing a substantially lower number of diffusion images.     

A framework for voxel-based morphometric analysis of the optic radiation using diffusion tensor imaging in glaucoma

Glaucoma is an optic neuropathy affecting the entire visual system. The understanding of the glaucoma mechanism and causes remains unresolved. Diffusion tensor imaging (DTI) has been used to analyze the optic nerve and optic radiation showing global fiber abnormalities associated with glaucoma. Nevertheless, the complex structure of the optic radiation and the limitations of DTI make the localization of the glaucoma effect a difficult task. The aim of this work is to establish a framework for the determination of the local changes of the optic radiation due to glaucoma using DTI. The proposed system utilizes a semiautomated algorithm to produce an efficient identification of the optic radiation. Segmented optic radiations are transformed to a unified space using shape-based nonrigid registration. Using the deformation fields that resulted from the registration, the maps of the diffusion tensor-derived parameters are transformed to the unified space. This allows for statistical voxel-wise analysis to produce significant abnormality maps. The proposed system is applied to a group of 13 glaucoma patients and a normal control group of 10 subjects. The groups are age matched to eliminate the age effect on the analysis. Diffusion-related parameters (axial, radial and mean diffusivities) and an anisotropy index (fractional anisotropy) are studied. The anisotropy analysis indicates that the majority of the significant voxels show decreased fractional anisotropy in the glaucoma patients compared with the control group. In addition, the significant regions are mainly distributed in the middle (in reference to anterior–posterior orientation) of the optic radiation. Glaucoma subjects have increased radial diffusivity and mean diffusivity significant voxels with a main concentration in the proximal part of the right optic radiation. The proposed analysis provides a framework to capture the significant local changes of the optic radiation due to glaucoma. The preliminary analysis suggests that the glaucomatous optic radiation may suffer from localized white matter degeneration. The framework facilitates further studies and understanding of the pathophysiology of glaucoma.