Diffusion Tensor Magnetic Resonance Imaging Scans Research Articles

Experimental Methodologies for the Visualization of Cardiac Myofiber Orientations within Perfusion‐fixed Human Hearts

Cardiac myofiber structure and organizations play critical roles in the electrical and mechanical properties of the heart. Diffusion tensor magnetic resonance imaging (DTMRI) has been a useful imaging modality to visualize the myocardial fiber orientation with emerging clinical application. DTMRI takes advantage of the limited diffusion of water along the cardiac fiber’s longitudinal axis and provides the dominant direction of diffusion [1]. Until recently, DTMRI usage was relatively limited to clinical imaging of white matter within the brain. While there are limitations for cardiac use in vivo, due to tissue displacement and non‐rigid deformation, DTMRI is becoming a powerful diagnostic tool to assess structural heart damage. The data can also be the input into numerous computational simulations of the heart’s electrical activities. The Visible Heart®; Laboratories at the University of Minnesota, in collaboration with Lifesource, an organ procurement organization, maintains a large collection of human hearts that were donated for research. These organs are received fresh and subsequently preserved with 10% buffered formalin in the approximate end‐diastolic state for future anatomical studies. For the present studies, the hearts were rinsed of formalin and completely submerged in an agarose gel in attitudinally correct positions. The hearts are next scanned in a clinical 3T MRI scanner using a diffusion tensor sequence. The raw DTMRI DICOM files are then reconstructed using Diffusion Toolkit and visualized in TrackVis software [2]. This outputs a 3‐dimensional model that allows for visualization of the relative orientations of the myocardial fibers. Whole heart tissue models can also be generated using Materialise Mimics software from these scans. MRI scans of a heart from a 50 year old male with a history of myocardial infarction can be seen in Figure 1. The DTMRI axial images (Figure 1C) provide insights relative to the orientations of the myocardial fibers; which can then be transformed into a 3D diagram (Figure 1D) of directional eigenvectors. Future work will be done to improve resolutions by extending the number of averages acquired during such scanning. Increasing resolution will allow us to assess structural heart damage stemming from myocardial injuries: e.g. from ablations or due to myocardial infarction. Additionally, we hope to combine DTMRI with cardiac tissue models to create a 3D print that highlight regional myocardial fiber orientations. The fiber orientations from the DTMRI scans can also be incorporated into computer simulations, which may help elucidate the activation pathways of the heart. In some cases today, DTMRI can be utilized clinically to improve one’s understanding of the conduction system of the heart, which has implications in lead placement for pacing and ablation procedures. Researchers and clinicians can learn critical information relative to cardiac anatomy from DTMRI.An overview of the methods used to generate a 3D reconstruction of diffusion tensor MRI data. The resulting image is further refined to remove extraneous dataFigure 1

Combining Diffusion Tensor Imaging and Susceptibility Weighted Imaging on the Substantia Nigra of 1-Methyl-4-Phenyl-1, 2, 3, 6-Tetrahydropyridine (MPTP)-induced Rhesus Monkey Model of Parkinson's Disease.

The aim of this study was to evaluate whether combining diffusion tensor magnetic resonance imaging (DTI) and susceptibility weighted imaging (SWI) techniques would provide a sensitive method for differentiating between 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced rhesus monkey model of Parkinson's disease (PD) and wild-type controls. Seventeen rhesus monkeys were divided into two groups. A series of intramuscular injections of either saline (control group, n = 8) or MPTP (0.2 mg/kg body weight; PD group, n = 9) were given to the monkeys, twice a week. Then, SWI and DTI scans were obtained from the monkeys with Siemens Magnetom Verio 3.0T superconductive MRI system. Region of interest analysis was performed on substantia nigra pars compacta (SNc) and substantia nigra pars reticulata (SNr). In addition, immunohistochemical staining of tyrosine hydroxylase was applied to assess degeneration of SN dopaminergic neurons. Monkeys in the PD group displayed mild to moderate motor symptoms assessed using Kurlan's scale. With SWI scans, decreased width of SNc but increased width of SNr was found in PD group monkeys compared to controls. Calculation of the ratios of widths of SNc and SNr to the anterior and posterior mesencephalic diameter also reflected narrower SNc but wider SNr than controls. Decreased SWI signal intensity of SNc and SNr suggested iron deposition in both subregions of SN. The DTI scans showed lower fractional anisotropy (FA) values in SNc of the PD group monkeys, while no change of FA values in SNr was detected. Immunohistochemical test displayed generalized loss of dopaminergic neurons in SN of PD group monkeys. Combining the use of DTI and SWI can provide a sensitive method for differentiating between MPTP-induced rhesus monkey model of PD and wild-type controls. This effective imaging modality might provide additional information for characteristic identification of PD at early stages, thus enhancing the ability to make early diagnosis, and monitor progression of the natural history and treatment effects.

Cognitive Function and 3-Tesla Magnetic Resonance Imaging Tractography of White Matter Hyperintensities in Elderly Persons

Background/Aims: This study used 3-Tesla magnetic resonance imaging (MRI) tractography to determine if there was an association between tracts crossing white matter hyperintensities (WMH) and cognitive function in elderly persons. Methods: Brain T2-weighted fluid-attenuated inversion recovery (FLAIR) and diffusion tensor MRI scans were acquired in participants above the age of 60 years. Twenty-six persons had WMH identified on T2 FLAIR scans. They completed a battery of neuropsychological tests and were classified as normal controls (n = 15) or with Alzheimer's dementia (n = 11). Tractography was generated by the Fiber Assignment by Continuous Tracking method. All tracts that crossed WMH were segmented. The average fractional anisotropy and average mean diffusivity of these tracts were quantified. We studied the association between cognitive test scores with the average mean diffusivity and average fractional anisotropy of tracts while controlling for age, total WMH volume and diagnosis. Results: An increased mean diffusivity of tracts crossing WMH was associated with worse performance on the Wechsler Memory Scale-III Longest Span Forward (p = 0.02). There was no association between the fractional anisotropy of tracts and performance on cognitive testing. Conclusion: The mean diffusivity of tracts crossing WMH measured by tractography is a novel correlate of performance on the Wechsler Memory Scale-III Longest Span Forward in elderly persons.

Diffusion tensor magnetic resonance imaging in very early onset pediatric multiple sclerosis

Objectives: Active myelination during childhood may influence the impact of multiple sclerosis (MS) on brain structural integrity. We studied normal-appearing white matter (NAWM) in children with MS onset before age 12 years using diffusion tensor (DT) magnetic resonance imaging (MRI). Methods: DT MRI scans were obtained from 22 MS children with their first attack before age 12 years, and 31 healthy controls from two referral centers. Using probabilistic tractography, brain tissue integrity within interhemispheric, intrahemispheric, and projection tracts was compared between patients and site-matched controls. The impact of disease and age at MRI on tract NAWM fractional anisotropy (FA) and mean diffusivity (MD) values was evaluated using linear models. Results: Compared to controls, pediatric MS patients had reduced FA and increased MD of the bilateral superior longitudinal fasciculus and corpus callosum (CC), without center-by-group interaction. CC NAWM average FA was correlated with brain T2 lesion volume. In controls, the majority of the tracts analyzed showed a significant increase of FA and decrease of MD with age. Such a linear correlation was lost in patients. Conclusions: In very young pediatric MS patients, DT MRI abnormalities affect brain WM tracts differentially, and are only partially correlated with focal WM lesions. Impaired maturation of WM tracts with age may be an additional factor contributing to these findings.

White matter microstructure abnormalities in pediatric migraine patients.

Diffusion tensor (DT) magnetic resonance imaging (MRI) provides several quantities with the potential to disclose white matter (WM) microstructural abnormalities. We explored alterations of WM architecture in pediatric migraine patients using DT MRI and two different methods of analysis. Dual-echo and DT MRI scans were acquired from 15 pediatric migraine patients and 15 age-matched controls. Whole-brain voxel-wise comparisons of WM DT MRI abnormalities were performed using tract-based-spatial-statistics (TBSS). A DT probabilistic tractography analysis was also run. Both TBSS and DT tractography analysis showed that, compared to controls, pediatric migraine patients had significant lower mean (MD), axial (AD) and radial (RD) diffusivity of WM tracts located in the brainstem, thalamus and fronto-temporo-occipital lobes, bilaterally. Patients also experienced increased fractional anisotropy (FA) of the optic radiations. No correlation was found between WM tract abnormalities and disease duration and attack frequency. Pediatric migraine patients harbor diffuse brain WM microstructural abnormalities. High FA and low MD, AD and RD in these patients might be explained by repeated neuronal activation, which may lead to cell swelling and stimulate activity-dependent myelin-modulation, or by increased fiber and dendritic densities. Both these mechanisms might reflect a hyperexcitability of the brain in migraineurs.

Conditional Tat protein brain expression in the GT-tg bigenic mouse induces cerebral fractional anisotropy abnormalities.

Cerebral white matter changes including tissue water diffusion abnormalities detected with diffusion tensor magnetic resonance imaging (DTI) are commonly found in humans with Human Immunodeficiency Virus (HIV) infection, as well as in animal models of the disorder. The severities of some of these abnormalities have been reported to correlate with measures of disease progression or severity, or with the degree of cognitive dysfunction. Accordingly, DTI may be a useful translational biomarker. HIV-Tat protein appears to be an important factor in the viral pathogenesis of HIV-associated neurotoxicity. We previously reported cerebral gray matter density reductions in the GT-tg bigenic mouse treated with doxycycline (Dox) to conditionally induce Tat protein expression. Presently, we administered intraperitoneal (i.p.) Dox (100 mg/kg/day) for 7 days to GT-tg mice to determine whether induction of conditional Tat expression led to the development of cerebral DTI abnormalities. Perfused and fixed brains from eight GT-tg mice administered Dox and eight control mice administered saline i.p. were extracted and underwent DTI scans on a 9.4 Tesla scanner. A whole brain analysis detected fractional anisotropy (FA) reductions in several areas including insular and endopiriform regions, as well as within the dorsal striatum. These findings suggest that exposure to Tat protein is sufficient to induce FA abnormalities, and further support the use of the GT-tg mouse to model some effects of HIV.

Gliovascular disruption and cognitive deficits in a mouse model with features of small vessel disease.

Cerebral small vessel disease (SVD) is a major cause of age-related cognitive impairment and dementia. The pathophysiology of SVD is not well understood and is hampered by a limited range of relevant animal models. Here, we describe gliovascular alterations and cognitive deficits in a mouse model of sustained cerebral hypoperfusion with features of SVD (microinfarcts, hemorrhage, white matter disruption) induced by bilateral common carotid stenosis. Multiple features of SVD were determined on T2-weighted and diffusion-tensor magnetic resonance imaging scans and confirmed by pathologic assessment. These features, which were absent in sham controls, included multiple T2-hyperintense infarcts and T2-hypointense hemosiderin-like regions in subcortical nuclei plus increased cerebral atrophy compared with controls. Fractional anisotropy was also significantly reduced in several white matter structures including the corpus callosum. Investigation of gliovascular changes revealed a marked increase in microvessel diameter, vascular wall disruption, fibrinoid necrosis, hemorrhage, and blood-brain barrier alterations. Widespread reactive gliosis, including displacement of the astrocytic water channel, aquaporin 4, was observed. Hypoperfused mice also demonstrated deficits in spatial working and reference memory tasks. Overall, gliovascular disruption is a prominent feature of this mouse, which could provide a useful model for early-phase testing of potential SVD treatment strategies.

Genetic contributions to changes of fiber tracts of ventral visual stream in 22q11.2 deletion syndrome

Patients with 22q11.2 deletion syndrome (22q11.2DS) represent a population at high risk for developing schizophrenia, as well as learning disabilities. Deficits in visuo-spatial memory are thought to underlie some of the cognitive disabilities. Neuronal substrates of visuo-spatial memory include the inferior fronto-occipital fasciculus (IFOF) and the inferior longitudinal fasciculus (ILF), two tracts that comprise the ventral visual stream. Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) is an established method to evaluate white matter (WM) connections in vivo. DT-MRI scans of nine 22q11.2DS young adults and nine matched healthy subjects were acquired. Tractography of the IFOF and the ILF was performed. DT-MRI indices, including Fractional anisotropy (FA, measure of WM changes), axial diffusivity (AD, measure of axonal changes) and radial diffusivity (RD, measure of myelin changes) of each of the tracts and each group were measured and compared. The 22q11.2DS group showed statistically significant reductions of FA in IFOF in the left hemisphere. Additionally, reductions of AD were found in the IFOF and the ILF in both hemispheres. These findings might be the consequence of axonal changes, which is possibly due to fewer, thinner, or less organized fibers. No changes in RD were detected in any of the tracts delineated, which is in contrast to findings in schizophrenia patients where increases in RD are believed to be indicative of demyelination. We conclude that reduced axonal changes may be key to understanding the underlying pathology of WM leading to the visuo-spatial phenotype in 22q11.2DS.

Diffusion Tensor Magnetic Resonance Imaging in Patients with Multiple Sclerosis and its Relationship with Disability

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system. Diffusion tensor magnetic resonance imaging (DTI) can yield important information on the in vivo pathological processes affecting water diffusion. The aim of this study was to quantitatively define water diffusion in normal-appearing white matter (NAWM) distant from the plaque, in the plaque, and around the plaque, and to investigate the correlation of these changes with clinical disability. Conventional MRI and DTI scans were conducted in 30 patients with MS and 15 healthy individuals. Fractional anisotropy maps and visible diffusion coefficients were created and integrated with T2-weighted images. Regions of interest (ROIs) were placed on the plaques on the same side, white matter around the plaques and NAWM on the opposite side. Only the white matter of healthy individuals in the control group, and FA and ADC values were obtained for comparison. The highest FA and lowest ADC were detected in the control group at the periventricular region, cerebellar peduncle and at all ROIs irrespective of location. There was a significant difference in comparison to the control group at all ROIs in patients with MS (p < 0.001 for all comparisons). No significant correlation between diffusion parameters and expanded disability state scale (EDSS) scores was found in patients with MS. DTI may provide more accurate information on the damage due to the illness, compared to T2A sequences, but this damage may not be correlated with the clinical disability measured by EDSS score.

Atlas‐Based Versus Individual‐Based Fiber Tracking of the Corpus Callosum in Patients with Multiple Sclerosis: Reliability and Clinical Correlations

In multiple sclerosis (MS), the presence of lesions and normal-appearing white matter damage may affect the reliability of diffusion tensor (DT) magnetic resonance imaging (MRI)-based tractography. We compared the performance of an individual-based method for corpus callosum (CC) fiber tracking in MS with those of two atlas-based methods. Brain DT MRI scans were acquired from 35 patients with MS and 18 age-matched healthy volunteers (HV). DT-derived metrics from the CC-the mean diffusivity (MD) and fractional anisotropy (FA)-were calculated using an individual-based and two atlas-based methods with different types of subject registration (linear and nonlinear) to a CC atlas. Customized termination criteria were applied to stop the tracking algorithm when using the individual-based method. All the methods were able to distinguish between MS patients and HV. Using the individual-based method, stronger relationships were found between CC DT-derived metrics and the subjects' clinical condition. CC DT tractography using an individual-based method is more sensitive than the atlas-based ones to tract-specific alterations related to MS disability. An atlas-based method with nonlinear registration can be a valid alternative when an automated postprocessing is warranted, such as in the case of high volumes of data.

Co-registration of White Matter Tractographies by Adaptive-Mean-Shift and Gaussian Mixture Modeling

In this paper, we present a robust approach to the registration of white matter tractographies extracted from diffusion tensor-magnetic resonance imaging scans. The fibers are projected into a high dimensional feature space based on the sequence of their 3-D coordinates. Adaptive mean-shift clustering is applied to extract a compact set of representative fiber-modes (FM). Each FM is assigned to a multivariate Gaussian distribution according to its population thereby leading to a Gaussian mixture model (GMM) representation for the entire set of fibers. The registration between two fiber sets is treated as the alignment of two GMMs and is performed by maximizing their correlation ratio. A nine-parameters affine transform is recovered and eventually refined to a twelve-parameters affine transform using an innovative mean-shift based registration refinement scheme presented in this paper. The validation of the algorithm on synthetic intrasubject data demonstrates its robustness to interrupted and deviating fiber artifacts as well as outliers. Using real intrasubject data, a comparison is conducted to other intensity based and fiber-based registration algorithms, demonstrating competitive results. An option for tracking-in-time, on specific white matter fiber tracts, is also demonstrated on the real data.

Diffusion Tensor MRI in Multiple Sclerosis

During the last 10 years, thanks to the development of sophisticated acquisition schemes and the application of novel image analysis and postprocessing, diffusion tensor (DT) magnetic resonance imaging (MRI) has increasingly been applied to the study of multiple sclerosis (MS). DT MRI proved to be able to detect and quantify tissue damage within and outside T2-visible MS lesions. In addition, DT MRI has been shown to be sensitive to the evolution of MS damage over short-term periods of time, and therefore holds promise to provide us with in vivo correlates of MS clinical severity, as well as predictors of long-term disease evolution. Recent developments of the technique, such as DT tractography, are likely to improve dramatically our understanding of the mechanisms associated to the accumulation of MS disability. Unresolved issues to be addressed include the definition of the actual features underlying diffusion changes in MS and the potential of DT MRI in the differential diagnosis between MS and other demyelinating conditions. The best acquisition and postprocessing strategies for DT MRI studies of MS also remain a matter of debate. Moreover, the precision and accuracy of DT MRI scans in detecting longitudinal, MS-related changes need to be further investigated. This is a pivotal issue for a future application of DT MRI to the monitoring of MS evolution in large-scale clinical trials and, possibly, in individual patients.

Evidence for white matter disruption in traumatic brain injury without macroscopic lesions

Background: Non-missile traumatic brain injury (nmTBI) without macroscopically detectable lesions often results in cognitive impairments that negatively affect daily life. Aim: To identify abnormal white matter projections in patients with...

Robust unsupervised segmentation of infarct lesion from diffusion tensor MR images using multiscale statistical classification and partial volume voxel reclassification

Manual region tracing method for segmentation of infarction lesions in images from diffusion tensor magnetic resonance imaging (DT-MRI) is usually used in clinical works, but it is time consuming. A new unsupervised method has been developed, which is a multistage procedure, involving image preprocessing, calculation of tensor field and measurement of diffusion anisotropy, segmentation of infarction volume based on adaptive multiscale statistical classification (MSSC), and partial volume voxel reclassification (PVVR). The method accounts for random noise, intensity overlapping, partial volume effect (PVE), and intensity shading artifacts, which always appear in DT-MR images. The proposed method was applied to 20 patients with clinically diagnosed brain infarction by DT-MRI scans. The accuracy and reproducibility in terms of identifying the infarction lesion have been confirmed by clinical experts. This automatic segmentation method is promising not only in detecting the location and the size of infarction lesion in stroke patient but also in quantitatively analyzing diffusion anisotropy of lesion to guide clinical diagnoses and therapy.

Intra-voxel and inter-voxel coherence in patients with multiple sclerosis assessed using diffusion tensor MRI.

Previous diffusion tensor magnetic resonance imaging (DT-MRI) studies reported mean diffusivity () and fractional anisotropy (FA) changes in lesions and normal-appearing white matter (NAWM) of patients with multiple sclerosis (MS), but neglected the additional information which can be obtained by the analysis of the inter-voxel coherence (C). The present study is based on a large sample of patients with MS and it is aimed at assessing the potential role of C in the quantification of MS-related tissue damage of T2-visible lesions and NAWM. We obtained dual-echo, T1-weighted and DT-MRI scans from 78 patients with relapsing-remitting (RR), secondary progressive (SP), or primary progressive (PP) MS and from 26 healthy volunteers. We calculated, FA and C of T2-hyperintense lesions, T1-isointense lesions, T1-hypointense lesions and several areas of the NAWM. and FA of the majority of NAWM regions studied from MS patients were different from the corresponding quantities of the white matter from controls. NAWM C from patients was lower than white matter C from controls only for the parietal pericallosal areas. SPMS patients had higher corpus callosum and lower corpus callosum FA and C than patients with either RRMS or PPMS. Average lesion was higher, and average FA and C lower than the corresponding quantities measured in the NAWM. Average T1-hypointense lesion was higher and average FA lower than the corresponding quantities of T1-isointense lesions, whereas average C of these two lesion populations were not different. SPMS had higher average lesion than both PPMS and RRMS patients. NAWM and C of the corpus callosum were moderately correlated with disability. This study confirms the role of DT-MRI metrics to identify MS lesions with different amounts of tissue damage and to detect diffuse changes in the NAWM. It also shows that measuring C enables us to obtain additional information about tissue damage, which is complementary to that given by the analysis of and FA.

White matter damage in Alzheimer's disease assessed in vivo using diffusion tensor magnetic resonance imaging

Objective: To investigate the extent and the nature of white matter tissue damage of patients with Alzheimer's disease using diffusion tensor magnetic resonance imaging (DT-MRI). Background: Although Alzheimer's disease pathology...