Diffusion Tensor Imaging Protocol Research Articles

Diffusion tensor imaging of liver fibrosis in an experimental model

To characterize changes in diffusion properties of liver using diffusion tensor imaging (DTI) in an experimental model of liver fibrosis. Liver fibrosis was induced in Sprague-Dawley rats (n = 12) by repetitive dosing of carbon tetrachloride (CCl(4)). The animals were examined with a respiratory-gated single-shot spin-echo echo-planar DTI protocol at 7 T before, 2 weeks after, and 4 weeks after CCl(4) insult. Apparent diffusion coefficient (ADC), directional diffusivities (ADC(//) and ADC(⊥)), and fractional anisotropy (FA) were measured. Liver histology was performed with hematoxylin-eosin staining and Masson's trichrome staining. Significant decrease (P < 0.01) in ADC was found at 2 weeks (0.86 ± 0.09 × 10(-3) mm(2)/s) and 4 weeks (0.74 ± 0.09 × 10(-3) mm(2)/s) following CCl(4) insult, as compared with that before insult (0.97 ± 0.08 × 10(-3) mm(2)/s). Meanwhile, FA at 2 weeks (0.18 ± 0.03) after CCl(4) insult was significantly lower (P < 0.01) than that before insult (0.26 ± 0.05), and subsequently normalized at 4 weeks (0.26 ± 0.07) after the insult. Histology showed collagen deposition, presence of intracellular fat vacuoles, and cell necrosis/apoptosis in livers with CCl(4) insult. DTI detected the progressive changes in water diffusivities and diffusion anisotropy of liver tissue in this liver fibrosis model. ADC and FA are potentially valuable in detecting liver fibrosis at early stages and monitoring its progression. Future human studies are warranted to further verify the applicability of DTI in characterizing liver fibrosis and to determine its role in clinical settings.

The Correlation of 3D DT-MRI Fiber Disruption with Structural and Mechanical Degeneration in Porcine Myocardium

Evaluation of structural parameters following a myocardial infarction (MI) is important to assess left ventricular function and remodeling. In this study, we assessed the capability of 3D diffusion tensor magnetic resonance imaging (DT-MRI) to assess tissue degeneration shortly after an MI using a porcine model of infarction. Two days after an induced infarction, hearts were explanted and immediately scanned by a 3T MRI scanner with a diffusion tensor imaging protocol. 3D fiber tracks and clustering models were generated from the diffusion-weighted imaging data. We found in a normal explanted heart that DT-MRI fibers showed a multilayered helical structure, with fiber architecture and fiber density reflecting the integrity of muscle fibers. For infarcted heart explants, we observed either a lack of fibers or disruption of fibers in the infarcted regions. Contours of the disrupted DT-MRI fibers were found to be consistent with the infarcted regions. Both histological and mechanical analysis of the infarcted hearts suggested DT-MRI fiber disruption correlated with altered microstructure and tissue mechanics. The ability of 3D DT-MRI to accurately distinguish viable myocardium from dead myocardium only 2days post infarct without the use of radioisotopes or ionotropic agents makes it a promising approach to evaluate cardiac damage early post-MI.

Identical, but not the same: Intra-site and inter-site reproducibility of fractional anisotropy measures on two 3.0 T scanners

Diffusion Tensor Imaging (DTI) is being increasingly used to assess white matter integrity and it is therefore paramount to address the test–retest reliability of DTI measures. In this study we assessed inter- and intra-site reproducibility of two nominally identical 3T scanners at different sites in nine healthy controls using a DTI protocol representative of typical current “best practice” including cardiac gating, a multichannel head coil, parallel imaging and optimized diffusion gradient parameters. We calculated coefficients of variation (CV) and intraclass correlation coefficients (ICC) of fractional anisotropy (FA) measures for the whole brain, for three regions of interest (ROI) and for three tracts derived from these ROI by probabilistic tracking. We assessed the impact of affine, nonlinear and template based methods for spatially aligning FA maps on the reproducibility. The intra-site CV for FA ranged from 0.8% to 3.0% with ICC from 0.90 to 0.99, while the inter-site CV ranged from 1.0% to 4.1% with ICC of 0.82 to 0.99. Nonlinear image coregistration improved reproducibility compared to affine coregistration. Normalization to template space reduced the between-subject variation, resulting in lower ICC values and indicating a possibly reduced sensitivity. CV from probabilistic tractography were about 50% higher than for the corresponding seed ROI.Reproducibility maps of the whole scan volume showed a low variation of less than 5% in the major white matter tracts but higher variations of 10–15% in gray matter regions.One of the two scanners showed better intra-site reproducibility, while the intra-site CV for both scanners was significantly better than inter-site CV. However, when using nonlinear coregistration of FA maps, the average inter-site CV was below 2%. There was a consistent inter-site bias, FA values on site 2 were 1.0–1.5% lower than on site 1. Correction for this bias with a global scaling factor reduced the inter-site CV to the range of intra-site CV. Our results are encouraging for multi-centre DTI studies in larger populations, but also illustrate the importance of the image processing pipeline for reproducibility.

Toward a practical protocol for human optic nerve DTI with EPI geometric distortion correction

To develop a practical protocol for diffusion tensor imaging (DTI) of the human optic nerve with echo planar imaging (EPI) geometric distortion correction. A conventional DTI protocol was modified to acquire images with fat and cerebrospinal fluid (CSF) suppression and field inhomogeneity maps of contiguous coronal slices covering the whole brain. The technique was applied to healthy volunteers and multiple sclerosis patients with and without a history of unilateral optic neuritis. DTI measures and optic nerve tractography before and after geometric distortion correction were compared. Diffusion measures from left and right or from affected and unaffected eyes in different subject cohorts were reported. The image geometry after correction closely resembled reference anatomical images. Optic nerve tractography became feasible after distortion correction. The diffusion measures from the healthy volunteers were in good agreement with the literature. Statistically significant differences were found in the fractional anisotropy and orthogonal eigenvalues between affected and unaffected eyes in optic neuritis patients with poor recovery. The diffusion measures before and after geometric distortion correction were not significantly different. For cohorts without optic neuritis, the difference between diffusion measures from left and right eyes was not statistically significant. The proposed technique could provide a practical DTI protocol to study the human optic nerve.

Evaluating regional blood spinal cord barrier dysfunction following spinal cord injury using longitudinal dynamic contrast-enhanced MRI

BackgroundIn vivo preclinical imaging of spinal cord injury (SCI) in rodent models provides clinically relevant information in translational research. This paper uses multimodal magnetic resonance imaging (MRI) to investigate neurovascular pathology and changes in blood spinal cord barrier (BSCB) permeability following SCI in a mouse model of SCI.MethodsC57BL/6 female mice (n = 5) were subjected to contusive injury at the thoracic T11 level and scanned on post injury days 1 and 3 using anatomical, dynamic contrast-enhanced (DCE-MRI) and diffusion tensor imaging (DTI). The injured cords were evaluated postmortem with histopathological stains specific to neurovascular changes. A computational model was implemented to map local changes in barrier function from the contrast enhancement. The area and volume of spinal cord tissue with dysfunctional barrier were determined using semi-automatic segmentation.ResultsQuantitative maps derived from the acquired DCE-MRI data depicted the degree of BSCB permeability variations in injured spinal cords. At the injury sites, the damaged barriers occupied about 70% of the total cross section and 48% of the total volume on day 1, but the corresponding measurements were reduced to 55% and 25%, respectively on day 3. These changes implied spatio-temporal remodeling of microvasculature and its architecture in injured SC. Diffusion computations included longitudinal and transverse diffusivities and fractional anisotropy index. Comparison of permeability and diffusion measurements indicated regions of injured cords with dysfunctional barriers had structural changes in the form of greater axonal loss and demyelination, as supported by histopathologic assessments.ConclusionThe results from this study collectively demonstrated the feasibility of quantitatively mapping regional BSCB dysfunction in injured cord in mouse and obtaining complementary information about its structural integrity using in vivo DCE-MRI and DTI protocols. This capability is expected to play an important role in characterizing the neurovascular changes and reorganization following SCI in longitudinal preclinical experiments, but with potential clinical implications.

The use of novel gradient directions with DTI to synthesize data with complicated diffusion behavior

This study demonstrates a new technique for synthesizing diffusion tensor imaging (DTI) data sets that exhibit complex diffusion characteristics by performing operations on acquired DTI data of simple structures with anisotropic diffusive properties. The motivation behind this technique is to characterize the behavior of noise in complicated data using a phantom. Compared to simulations, an advantage to this approach is that the acquired data contain noise characteristic of the scanner and protocol. Using this technique, a simple capillary phantom is employed to infer the quality of data for more clinically realistic tissue structures (e.g., crossing fiber tracts). A water-filled phantom containing capillary arrays was constructed to demonstrate this technique, which uses a DTI protocol with typical clinical parameters. Eigenvalues and fractional anisotropy were calculated for the initial prolate data. Data were adjusted to synthesize different apparent diffusion coefficient (ADC) spatial distributions, which were compared to theoretical and analytical models. RMS differences and volumetric overlap between expected and measured ADC distributions were quantified for all synthesized distributions. Differences between synthesized and actual distributions were discussed.

Evaluation of measurement uncertainties in human diffusion tensor imaging (DTI)‐derived parameters and optimization of clinical DTI protocols with a wild bootstrap analysis

To quantify measurement uncertainties of fractional anisotropy, mean diffusivity, and principal eigenvector orientations in human diffusion tensor imaging (DTI) data acquired with common clinical protocols using a wild bootstrap analysis, and to establish optimal scan protocols for clinical DTI acquisitions. A group of 13 healthy volunteers were scanned using three commonly used DTI protocols with similar total scan times. Two important parameters-the number of unique diffusion gradient directions (NUDG) and the ratio of the total number of diffusion-weighted (DW) images to the total number of non-DW images (DTIR)-were analyzed in order to investigate their combined effects on uncertainties of DTI-derived parameters, using results from both the Monte Carlo simulation and the wild bootstrap analysis of uncertainties in human DTI data. The wild bootstrap analysis showed that uncertainties in human DTI data are significantly affected by both NUDG and DTIR in many brain regions. These results agree with previous predictions based on error-propagations as well as results from simulations. Our results demonstrate that within a clinically feasible DTI scan time of about 10 minutes, a protocol with number of diffusion gradient directions close to 30 provides nearly optimal measurement results when combined with a ratio of the total number of DW images over non-DW images equal to six. Wild bootstrap can serve as a useful tool to quantify the measurement uncertainty from human DTI data.

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.

Diffusion tensor imaging tractography and reliability analysis for limbic and paralimbic white matter tracts

Diffusion tensor imaging (DTI) provides the opportunity to study white matter tracts in vivo. The goal was to estimate the reliability of DTI tractography for the analysis of limbic and paralimbic white matter. Normative data from 24 healthy subjects and reliability data from four healthy and four depressed subjects were acquired at 1.5 Tesla, using twice-refocused spin-echo, echoplanar DTI and Fluid-Attenuated Inversion Recovery (FLAIR) DTI sequences. Fiber tracking was performed using the Fiber Assignment by Continuous Tracking algorithm. Fractional Anisotropy (FA), trace Apparent Diffusion Coefficient and tract volumes were calculated. The inter-rater (and intra-rater) intraclass correlation coefficients for FA values were as follows: rostral cingulum 0.89 (0.87), dorsal cingulum 0.85 (0.90), parahippocampal cingulum 0.85 (0.95), uncinate fasciculus 0.85 (0.87), medial prefrontal white matter 0.97 (0.99), ventromedial prefrontal white matter 0.92 (0.93), crus of fornix 0.80 (0.81). The reported DTI protocol provides a reliable method to analyze limbic and paralimbic white matter tracts relevant to psychiatric disorders.

Influence of steady background gradients on the accuracy of molecular diffusion anisotropy measurements

Spatial susceptibility variations of body components lead to local gradients of the static magnetic field. Effects of such background gradients on fractional diffusion anisotropy (FA) measurements on whole-body magnetic resonance units operating at 1.5, 3.0 and 7.0 T were analyzed theoretically and experimentally. Analytical expressions were derived for the cases of diffusion occurring in isotropic media and in tissues with cylindrical symmetry (e.g., white matter tracts or skeletal musculature). Typical magnitudes of background gradient strengths were estimated from in vivo and in vitro measurements with B0 field mapping sequences. Additionally, numerical simulations of magnetic field distributions and resulting field gradients were performed considering tissue-air interfaces in simplified geometrical arrangements. For media with isotropic diffusion, both measurements and analytical calculations showed increasing FA inaccuracy with stronger coupling between diffusion-encoding and background gradients. For cylindrical symmetry, FA values were estimated for a standard diffusion tensor imaging protocol in a realistic scenario. At 1 mm distance from a water-air interface, susceptibility-related background gradients amount to approximately 9 mT/m at 7 T and lead to a relative error of the measured FA of up to 48%. The error in the anisotropy assessment rises considerably with increasing field strength and must be taken into account especially for experimental and clinical studies on modern high-field systems.

An optimized wild bootstrap method for evaluation of measurement uncertainties of DTI-derived parameters in human brain

Evaluation of measurement uncertainties (or errors) in diffusion tensor-derived parameters is essential to quantify the sensitivity and specificity of these quantities as potential surrogate biomarkers for pathophysiological processes with diffusion tensor imaging (DTI). Computational methods such as the Monte Carlo simulation have provided insights into characterization of the measurement uncertainty in DTI. However, due to the complexity of real brain data as well as different sources of variations during the image acquisition, a robust estimator for DTI measurement uncertainty in human brain is required. Recent studies have shown that wild bootstrap, a novel nonparametric statistical method, can potentially provide effective estimations of DTI measurement uncertainties in human brain DTI data. In this study, we further optimized the DTI application of the wild bootstrap method for typical clinical applications. We evaluated the validity of wild bootstrap utilizing numerical simulations with different combinations of DTI protocol parameters and wild bootstrap experimental designs, and quantitatively compared estimates of uncertainties from wild bootstrapping with those from Monte Carlo simulations. Our results demonstrate that a wild bootstrap implementation using at least 1000 wild bootstrap iterations with a type II or type III heteroskedasticity consistent covariance matrix estimator provides robust evaluations of most DTI protocols.

Diffusion Tensor Imaging of the Spinal Cord at 1.5 and 3.0 Tesla

The feasibility of highly resolved diffusion tensor imaging (DTI) of the human cervical spinal cord was tested on a clinical MR unit operating at 3.0 Tesla. DTI parametrical maps and signal-to-noise ratios (SNRs) were compared to results recorded at 1.5 Tesla. Eight healthy volunteers and one patient participated in the study. A transverse oriented single-shot ECG-triggered echo-planar imaging (EPI) sequence with double spin-echo diffusion preparation was applied for highly resolved DTI of the spinal cord. The signal yield, fractional anisotropy (FA), and mean diffusivity (MD) were compared for both field strengths. The clinical applicability of the protocol was also tested in one patient with amyotrophic lateral sclerosis (ALS) at 3.0 T. A mean increase in SNR of 95.7 +/- 4.6 % was found at 3.0 Tesla compared to 1.5 Tesla. Improved quality of the DTI parametrical maps was observed at higher field strength (p < 0.02). Comparable FA and MD (reported in units of 10 (-3) mm (2)/s) values were computed in the dorsal white matter at both field strengths (1.5 T: FA = 0.75 +/- 0.08, MD = 0.84 +/- 0.12, 3.0 T: FA = 0.74 +/- 0.04, MD = 0.93 +/- 0.14). The DTI images exhibited diagnostic image quality in the patient. At the site of the diseased corticospinal tract, a decrease of 46.0 +/- 3.8 % in FA (0.40 +/- 0.03) and an increase of 50.3 +/- 5.6 % in MD (1.40 +/- 0.05) were found in the ALS patient. The 3.0 Tesla field strength provides higher image quality in DTI of the spinal cord compared to 1.5 T. The proposed DTI protocol seems adequate for the assessment of spinal cord diseases.

In vivo fiber tracking in the rat brain on a clinical 3T MRI system using a high strength insert gradient coil

In vivo neuroimaging methods permit longitudinal quantitative examination of the dynamic course of neurodegenerative conditions in humans and animal models and enable assessment of therapeutic efforts in mitigating disease effects on brain systems. The study of conditions affecting white matter, such as multiple sclerosis, demyelinating conditions, and drug and alcohol dependence, can be accomplished with diffusion tensor imaging (DTI), a technique uniquely capable of probing the microstructural integrity of white matter fibers in the living brain. We used a 3T clinical MR scanner equipped with an insert gradient coil that yields an order of magnitude increase in performance over the whole-body hardware to acquire in vivo DTI images of rat brain. The resolution allowed for fiber tracking evaluation of fractional anisotropy (FA) and apparent diffusion coefficients in the genu and splenium of the corpus callosum. A comparison of short (46 min) and long (92 min) acquisition time DTI protocols indicated low but adequate signal-to-noise ratio (SNR=6.2) of the shorter protocol to conduct quantitative fiber tracking enhanced by multiple acquisitions. As observed in human studies, FA in the rat splenium was higher than in the genu. Advantages of this technology include the use of similar user interface, pulse sequences, and field strength for preclinical animal and clinical human research, enhancing translational capabilities. An additional benefit of scanning at lower field strength, such as 3 T, is the reduction of artifacts due to main field inhomogeneity relative to higher field animal systems.

Diffusion tensor imaging in children and adolescents: Reproducibility, hemispheric, and age-related differences

We evaluated intra-rater, inter-rater, and between-scan reproducibility, hemispheric differences, and the effect of age on apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in healthy children (age range 5.5–19.1 years) examined with a clinical diffusion tensor imaging (DTI) protocol at 1.5 T, using a region of interest (ROI) methodology. Measures of reliability and precision were assessed in six ROIs using two different ROI shapes (polygonal and ellipsoidal). Results: Highly reproducible values of ADC and FA were obtained with the polygonal method on intra-rater (coefficients of variation ≤ 2.7%) and inter-rater (coefficients of variation ≤ 4.8%) reproducibility. For between-scan reproducibility, the coefficients of variation were ≤ 5.0%. Mean asymmetry indices were in the range from − 4% to 9% for FA and from − 6% to 3% for ADC. ADC showed significant negative correlation with age in 13 of 15 examined fiber tracts and FA increased significantly in three fiber tracts. Our results show that the evaluated DTI protocol is suitable for clinical application in pediatric population.

Use of capillaries in the construction of an MRI phantom for the assessment of diffusion tensor imaging: demonstration of performance

Although diffusion tensor imaging (DTI) shows great potential for the diagnosis of a variety of pathologies, no consensus for an appropriate assessment standard of DTI exists. This study examined the feasibility of using water-filled arrays of glass capillaries to construct a DTI phantom suitable for making repeated and reproducible measurements required in a quality assessment program. Three phantoms were constructed using arrays of capillaries with three inner diameters (23, 48, and 82 microm). Data were acquired using DTI protocols; the fractional anisotropy (FA), mean apparent diffusion coefficient (ADC) and principal eigenvectors of the diffusion tensors were calculated. This study demonstrated four results: (1) echo-planar images show that susceptibility within the capillary arrays does not lead to substantial differences in precessional frequency in regions containing the arrays and neither do the regions show noticeable image distortion; (2) principal eigenvectors of the diffusion tensors agree to within<10.3 degrees of the array orientations; (3) mean FA values (0.18-0.50) and ADC values (1.40-1.93x10-(3) mm2/s) within specified regions of interest are in general agreement with simulations after a simple noise correction; and (4) these array performance characteristics are observable using a typical clinical DTI protocol.

Adolescents with Disruptive Behavior Disorder Investigated Using an Optimized MR Diffusion Tensor Imaging Protocol

Adolescents with disruptive behavior disorder (DBD) and controls were investigated using an optimized MR diffusion tensor imaging (DTI) protocol in order to assess any possible structural abnormalities associated with DBD. Thirty-six patients and 40 normal subjects were examined. The extracted diffusion fractional anisotropy (FA) results demonstrate that for the DBD patients there is significantly reduced FA in both the frontal and left temporal regions. The largest brain area with significantly reduced FA is located within the arcuate fasciculus, which has projections extending from the temporal lobe to the frontal lobe along the lateral ventricle, lateral to the tapetum. The reduced FA reflects directly a lower extent of myelination and less coherent fiber track structures in the fasciculus, which in turn may indicate communication weakness among the associated cortical areas. The detected white matter microstructural abnormality, therefore, may be related to the developmental deficits observed in the patient group.

K‐space correction of eddy‐current‐induced distortions in diffusion‐weighted echo‐planar imaging

This paper describes a method for correcting eddy-current (EC)-induced distortions in diffusion-weighted echo-planar imaging (DW-EPI). First, reference measurements of EC fields within the EPI acquisition window are performed for DW gradient pulses applied separately along each physical axis of the gradient set and for a range of gradient amplitudes. EC fields caused by the DW gradients of the DW-MRI protocol are then calculated using the reference EC measurements. Finally, these calculated fields are used to correct the respective DW-EPI raw (k-space) data during image reconstruction. The technique was implemented in a small-bore MRI scanner with no digital preemphasis. It corrected EC-induced image distortions in both phantom and in vivo brain diffusion tensor imaging (DTI) data more effectively than commonly used image-based techniques. The method did not increase imaging time, since the same reference EC measurements were used to correct data acquired from different phantoms, subjects, and DTI protocols. Because of the simplicity of the reference EC measurements, the method can easily be implemented in clinical scanners.

A Comparative Study of Acquisition Schemes for Diffusion Tensor Imaging Using MRI

This study has investigated the effects of the selection of the diffusion-weighted (DW) gradient directions on the precision of a diffusion tensor imaging (DTI) experiment. The theoretical analysis provided a quantitative framework in which the noise performance of DTI schemes could be assessed objectively and for the development of novel DTI schemes, which employ multiple DW gradient directions. This generic framework was first applied to the examination of two commonly used DTI schemes, which employed 6 DW gradient directions and hitherto were used indiscriminately under the sole condition of noncollinearity. It was then used to design and assess a novel 12-DW-gradient-direction DTI protocol, which employed the same total number of DW acquisitions as the two conventional schemes (12). This theoretical investigation was then corroborated using rigorous simulation and DTI experiments on both an isotropic phantom and a healthy human brain. Both the theoretical and the experimental analysis demonstrated that the two conventional schemes showed a significantly different noise performance and that use of the new multiple-DW-gradient-direction scheme clearly improved the precision of the DTI measurements.