Stephan E. Maier

Processing and visualization for diffusion tensor MRI

This paper presents processing and visualization techniques for Diffusion Tensor Magnetic Resonance Imaging (DT-MRI). In DT-MRI, each voxel is assigned a tensor that describes local water diffusion. The geometric nature of diffusion tensors enables us to quantitatively characterize the local structure in tissues such as bone, muscle, and white matter of the brain. This makes DT-MRI an interesting modality for image analysis. In this paper we present a novel analytical solution to the Stejskal-Tanner diffusion equation system whereby a dual tensor basis, derived from the diffusion sensitizing gradient configuration, eliminates the need to solve this equation for each voxel. We further describe decomposition of the diffusion tensor based on its symmetrical properties, which in turn describe the geometry of the diffusion ellipsoid. A simple anisotropy measure follows naturally from this analysis. We describe how the geometry or shape of the tensor can be visualized using a coloring scheme based on the derived shape measures. In addition, we demonstrate that human brain tensor data when filtered can effectively describe macrostructural diffusion, which is important in the assessment of fiber-tract organization. We also describe how white matter pathways can be monitored with the methods introduced in this paper. DT-MRI tractography is useful for demonstrating neural connectivity (in vivo) in healthy and diseased brain tissue.

Microstructural development of human newborn cerebral white matter assessed in vivo by diffusion tensor magnetic resonance imaging.

Alterations of the architecture of cerebral white matter in the developing human brain can affect cortical development and result in functional disabilities. A line scan diffusion-weighted magnetic resonance imaging (MRI) sequence with diffusion tensor analysis was applied to measure the apparent diffusion coefficient, to calculate relative anisotropy, and to delineate three-dimensional fiber architecture in cerebral white matter in preterm (n = 17) and full-term infants (n = 7). To assess effects of prematurity on cerebral white matter development, early gestation preterm infants (n = 10) were studied a second time at term. In the central white matter the mean apparent diffusion coefficient at 28 wk was high, 1.8 µm2/ms, and decreased toward term to 1.2 µm2/ms. In the posterior limb of the internal capsule, the mean apparent diffusion coefficients at both times were similar (1.2 versus 1.1 µm2/ms). Relative anisotropy was higher the closer birth was to term with greater absolute values in the internal capsule than in the central white matter. Preterm infants at term showed higher mean diffusion coefficients in the central white matter (1.4 ± 0.24 versus 1.15 ± 0.09 µm2/ms, p = 0.016) and lower relative anisotropy in both areas compared with full-term infants (white matter, 10.9 ± 0.6 versus 22.9 ± 3.0%, p = 0.001; internal capsule, 24.0 ± 4.44 versus 33.1 ± 0.6% p = 0.006). Nonmyelinated fibers in the corpus callosum were visible by diffusion tensor MRI as early as 28 wk; full-term and preterm infants at term showed marked differences in white matter fiber organization. The data indicate that quantitative assessment of water diffusion by diffusion tensor MRI provides insight into microstructural development in cerebral white matter in living infants.

DTI and MTR abnormalities in schizophrenia: Analysis of white matter integrity

Diffusion tensor imaging (DTI) studies in schizophrenia demonstrate lower anisotropic diffusion within white matter due either to loss of coherence of white matter fiber tracts, to changes in the number and/or density of interconnecting fiber tracts, or to changes in myelination, although methodology as well as localization of such changes differ between studies. The aim of this study is to localize and to specify further DTI abnormalities in schizophrenia by combining DTI with magnetization transfer imaging (MTI), a technique sensitive to myelin and axonal alterations in order to increase specificity of DTI findings. 21 chronic schizophrenics and 26 controls were scanned using Line-Scan-Diffusion-Imaging and T1-weighted techniques with and without a saturation pulse (MT). Diffusion information was used to normalize co-registered maps of fractional anisotropy (FA) and magnetization transfer ratio (MTR) to a study-specific template, using the multi-channel daemon algorithm, designed specifically to deal with multidirectional tensor information. Diffusion anisotropy was decreased in schizophrenia in the following brain regions: the fornix, the corpus callosum, bilaterally in the cingulum bundle, bilaterally in the superior occipito-frontal fasciculus, bilaterally in the internal capsule, in the right inferior occipito-frontal fasciculus and the left arcuate fasciculus. MTR maps demonstrated changes in the corpus callosum, fornix, right internal capsule, and the superior occipito-frontal fasciculus bilaterally; however, no changes were noted in the anterior cingulum bundle, the left internal capsule, the arcuate fasciculus, or inferior occipito-frontal fasciculus. In addition, the right posterior cingulum bundle showed MTR but not FA changes in schizophrenia. These findings suggest that, while some of the diffusion abnormalities in schizophrenia are likely due to abnormal coherence, or organization of the fiber tracts, some of these abnormalities may, in fact, be attributed to or coincide with myelin/axonal disruption.

Cingulate fasciculus integrity disruption in schizophrenia: a magnetic resonance diffusion tensor imaging study

Evidence suggests that a disruption in limbic system network integrity and, in particular, the cingulate gyrus (CG), may play a role in the pathophysiology of schizophrenia; however, the cingulum bundle (CB), the white matter tract furnishing both input and output to CG, and the most prominent white matter fiber tract in the limbic system, has not been evaluated in schizophrenia using the new technology of diffusion tensor imaging (DTI). We used line scan DTI to evaluate diffusion in the CB in 16 male schizophrenia patients and 18 male control subjects, group-matched for age, parental socioeconomic status, and handedness. We acquired 4-mm-thick coronal slices through the entire brain. Maps of fractional anisotropy (FA) were generated to quantify diffusion within the left and right CB on eight slices that included the central portion of the CB. Results showed group differences, bilaterally, in area and mean FA for CB, where patients showed smaller area and less anisotropy than controls. For patients, decreased left CB correlated significantly with attention and working memory measures as assessed by the Wisconsin Card Sorting Test. These data provide strong evidence for CB disruptions in schizophrenia, which may be related to disease-related attention and working memory abnormalities.

Multi-component apparent diffusion coefficients in human brain†

The signal decay with increasing b‐factor at fixed echo time from brain tissue in vivo has been measured using a line scan Stejskal–Tanner spin echo diffusion approach in eight healthy adult volunteers. The use of a 175 ms echo time and maximum gradient strengths of 10 mT/m allowed 64 b‐factors to be sampled, ranging from 5 to 6000 s/mm2, a maximum some three times larger than that typically used for diffusion imaging. The signal decay with b‐factor over this extended range showed a decidedly non‐exponential behavior well‐suited to biexponential modeling. Statistical analyses of the fitted biexponential parameters from over 125 brain voxels (15 × 15 × 1 mm3 volume) per volunteer yielded a mean volume fraction of 0.74 which decayed with a typical apparent diffusion coefficient around 1.4 µm2/ms. The remaining fraction had an apparent diffusion coefficient of approximately 0.25 µm2/ms. Simple models which might explain the non‐exponential behavior, such as intra‐ and extracellular water compartmentation with slow exchange, appear inadequate for a complete description. For typical diffusion imaging with b‐factors below 2000 s/mm2, the standard model of monoexponential signal decay with b‐factor, apparent diffusion coefficient values around 0.7 µm2/ms, and a sensitivity to diffusion gradient direction may appear appropriate. Over a more extended but readily accessible b‐factor range, however, the complexity of brain signal decay with b‐factor increases, offering a greater parametrization of the water diffusion process for tissue characterization. Copyright

Line scan diffusion imaging

A novel line scan diffusion imaging sequence (LSDI) is introduced. LSDI is inherently insensitive to motion artifacts and high quality diffusion maps of the brain can be obtained rapidly without the use of head restraints or cardiac gating. Results from a stroke study and abdominal diffusion images are presented. The results indicate that it is feasible to use the LSDI technique for clinical evaluation of acute ischemic stroke. In contrast to echo‐planar diffusion imaging, LSDI does not require modified gradient hardware and can be implemented on conventional scanners. Thus, LSDI should dramatically increase the general availability of robust clinical diffusion imaging.

White matter hemisphere asymmetries in healthy subjects and in schizophrenia: a diffusion tensor MRI study

Hemisphere asymmetry was explored in normal healthy subjects and in patients with schizophrenia using a novel voxel-based tensor analysis applied to fractional anisotropy (FA) of the diffusion tensor. Our voxel-based approach, which requires precise spatial normalization to remove the misalignment of fiber tracts, includes generating a symmetrical group average template of the diffusion tensor by applying nonlinear elastic warping of the demons algorithm. We then normalized all 32 diffusion tensor MRIs from healthy subjects and 23 from schizophrenic subjects to the symmetrical average template. For each brain, six channels of tensor component images and one T2-weighted image were used for registration to match tensor orientation and shape between images. A statistical evaluation of white matter asymmetry was then conducted on the normalized FA images and their flipped images. In controls, we found left-higher-than-right anisotropic asymmetry in the anterior part of the corpus callosum, cingulum bundle, the optic radiation, and the superior cerebellar peduncle, and right-higher-than-left anisotropic asymmetry in the anterior limb of the internal capsule and the anterior limbs prefrontal regions, in the uncinate fasciculus, and in the superior longitudinal fasciculus. In patients, the asymmetry was lower, although still present, in the cingulum bundle and the anterior corpus callosum, and not found in the anterior limb of the internal capsule, the uncinate fasciculus, and the superior cerebellar peduncle compared to healthy subjects. These findings of anisotropic asymmetry pattern differences between healthy controls and patients with schizophrenia are likely related to neurodevelopmental abnormalities in schizophrenia.

Early Detection of Response to Radiation Therapy in Patients With Brain Malignancies Using Conventional and High b-Value Diffusion-Weighted Magnetic Resonance Imaging

PURPOSE To study the feasibility of using diffusion-weighted magnetic resonance imaging (DWMRI), which is sensitive to the diffusion of water molecules in tissues, for detection of early tumor response to radiation therapy; and to evaluate the additional information obtained from high DWMRI, which is more sensitive to low-mobility water molecules (such as intracellular or bound water), in increasing the sensitivity to response. PATIENTS AND METHODS Standard MRI and DWMRI were acquired before and at regular intervals after initiating radiation therapy for 10 malignant brain lesions in eight patients. RESULTS One week posttherapy, three of six responding lesions showed an increase in the conventional DWMRI parameters. Another three responding lesions showed no change. Four nonresponding lesions showed a decrease or no change. The early change in the diffusion parameters was enhanced by using high DWMRI. When high DWMRI was used, all responding lesions showed increase in the diffusion parameter and all nonresponding lesions showed no change or decrease. Response was determined by standard MRI 7 weeks posttherapy. The changes in the diffusion parameters measured 1 week after initiating treatment were correlated with later tumor response or no response (P <.006). This correlation was increased to P <.0006 when high DWMRI was used. CONCLUSION The significant correlation between changes in diffusion parameters 1 week after initiating treatment and later tumor response or no response suggests the feasibility of using DWMRI for early, noninvasive prediction of tumor response. The ability to predict response may enable early termination of treatment in nonresponding patients, prevent additional toxicity, and allow for early changes in treatment.

Evaluation of left ventricular segmental wall motion in hypertrophic cardiomyopathy with myocardial tagging.

BackgroundSegmental wall motion was assessed noninvasively in eight patients with hypertrophic cardiomyopathy and six healthy volunteers by magnetic resonance myocardial tagging. Methods and ResultsLocalization scans were performed for determination of the true short-axis views of the left ventricle (double-angulated view). Spatial modulation of magnetization was used to produce a rectangular grid of landmarks. Distortion of the grid was assessed at end diastole, mid systole, and end systole with multiphase gradient echos. Image sets were acquired at three different planes, namely, the base, the equator, and the apex. Quantitative evaluation was carried out by computer-assisted image analysis. Each individual grid crossing point was identified automatically and the displacement calculated. A polar coordinate system with the center of gravity as motion reference point was chosen to assess fractional rotation and radial displacement at the endocardial, midwall, and epicardial layers of the septal, anterior, posterior, and inferior regions. A wringing motion of the left ventricle with a clockwise rotation of 5.0 ± 2.4° at the base and a counterclockwise rotation of −9.6 ± 2.9° at the apex was observed in control subjects. An equal rotation of 5.0 ± 2.5° at the base and a slightly reduced rotation of −7.3 ± 5.2° at the apex was found in patients with hypertrophic cardiomyopathy. A transmural gradient in fractional rotation and radial displacement was observed, with the highest values in the endocardial layer. Rotation in patients with hypertrophic cardiomyopathy was significantly less than in normal volunteers in the posterior region of the equatorial and apical planes. Furthermore, radial displacement was significantly reduced in the septum and inferior wall. In the anterior and posterior wall segments, a reduction of the radial displacement was observed only in the epicardium and midwall layers. ConclusionsMagnetic resonance myocardial tagging allows the noninvasive assessment of regional wall motion. Both in normal volunteers and in patients with hypertrophic cardiomyopathies, cardiac motion occurs in a complex mode, with the base and the apex rotating in opposite directions and the equatorial plane as a transitional zone (wringing motion). A reduced cardiac rotation can be observed in patients with hypertrophic cardiomyopathy mainly in the posterior region, whereas a reduced radial displacement is found in the inferior septal zone.

Spatial normalization of diffusion tensor MRI using multiple channels

Diffusion Tensor MRI (DT-MRI) can provide important in vivo information for the detection of brain abnormalities in diseases characterized by compromised neural connectivity. To quantify diffusion tensor abnormalities based on voxel-based statistical analysis, spatial normalization is required to minimize the anatomical variability between studied brain structures. In this article, we used a multiple input channel registration algorithm based on a demons algorithm and evaluated the spatial normalization of diffusion tensor image in terms of the input information used for registration. Registration was performed on 16 DT-MRI data sets using different combinations of the channels, including a channel of T2-weighted intensity, a channel of the fractional anisotropy, a channel of the difference of the first and second eigenvalues, two channels of the fractional anisotropy and the trace of tensor, three channels of the eigenvalues of the tensor, and the six channel tensor components. To evaluate the registration of tensor data, we defined two similarity measures, i.e., the endpoint divergence and the mean square error, which we applied to the fiber bundles of target images and registered images at the same seed points in white matter segmentation. We also evaluated the tensor registration by examining the voxel-by-voxel alignment of tensors in a sample of 15 normalized DT-MRIs. In all evaluations, nonlinear warping using six independent tensor components as input channels showed the best performance in effectively normalizing the tract morphology and tensor orientation. We also present a nonlinear method for creating a group diffusion tensor atlas using the average tensor field and the average deformation field, which we believe is a better approach than a strict linear one for representing both tensor distribution and morphological distribution of the population.