In vivo DTI evaluation of white matter tracts in rat spinal cord

PURPOSE: To determine whether differences in specific spinal cord white matter (WM) tracts can be detected with in vivo DTI. MATERIALS AND METHODS: In vivo DTI was performed on six rats at the lower thoracic region using a 4.7T magnet. Axial diffusion images were obtained with diffusion gradients applied in six independent directions, with low and high b-values equal to 0 and 692 seconds/mm(2), respectively. Regions of interest (ROIs) were selected corresponding to the major spinal cord tracts, including the dorsal cortical spinal tract (dCST), fasciculus gracilis (FG), rubrospinal tract (RST), vestibulospinal tract (VST), and reticulospinal tract (ReST). RESULTS: ANOVA demonstrated overall differences between tracts for all of the DTI parameters, including fractional anisotropy (FA), trace diffusion (Tr), longitudinal diffusivity (EL = lambda(1)), and transverse diffusivity (ET = (lambda(2) + lambda(3))/2). Similarly to previous ex vivo analyses, the spinal cord tract with the largest and most widely spaced axons (VST) had the largest EL and ET. CONCLUSION: The principal diffusivities appear to reflect axon morphologic differences between the WM tracts that are not as well appreciated with FA and Tr.     

Formalin fixation alters water diffusion coefficient magnitude but not anisotropy in infarcted brain.

This study was designed to determine whether formalin fixation alters diffusion parameters in the infarcted brain. Diffusion tensor images were obtained from anesthetized mice 1 hr after middle cerebral artery occlusion and repeated after formalin fixation of brains. In live animals, there was a significant decrease in the trace of the diffusion tensor (Tr(D)) in infarcted cortex and external capsule compared with contralateral brain areas, with no change in relative anisotropy (RA). After formalin fixation, Tr(D) was reduced 30-80%. However, the Tr(D) differential present in vivo between injured and healthy tissues was lost, with Tr(D) reduced to similar values in all tissues except for the edge of the cortical infarction, where it was lower than in surrounding tissues. RA values were unchanged after fixation. This study supports the preservation of diffusion anisotropy for both healthy and injured white matter in fixed mouse brain. However, the sensitivity of water diffusion in detecting tissue injury in vivo is not preserved in fixed tissues.     

Effects of number of diffusion gradient directions on derived diffusion tensor imaging indices in human brain

BACKGROUND AND PURPOSE: The effects of a number of diffusion-encoding gradient directions (NDGD) on diffusion tensor imaging (DTI) indices have been studied previously with theoretic analysis and numeric simulations. In this study, we made in vivo measurements in the human brain to compare different clinical scan protocols and to evaluate their effects on the calculated DTI indices. METHODS: Fifteen healthy volunteers were scanned with a 1.5T MR scanner. Single-shot DTI images were acquired using 3 protocols different in NDGD and number of excitations (NEX) for each direction (NDGD/NEX = 6/10, 21/3, 31/2). Means and standard error of mean (SEM) were calculated and compared in 6 regions of interest (ROIs) for mean diffusivity (D), fractional anisotropy (FA), diffusion tensor eigenvalues (lambda(1), lambda(2), and lambda(3)), and correlation coefficients (r) of these indices among the 3 DTI protocols. RESULTS: At the ROI level, no significant differences were found for the mean and SEM of D and FA among protocols (P > .05). The 6-NDGD protocol, however, yielded higher values for lambda(1) and lambda(2) and lower values for lambda(3) in most ROIs (P < .05) compared with the other protocols. At the voxel level, the correlation between the protocols r(21-31) were higher than r(6-21) and r(6-31) in most ROIs. The correlation of FA among 3 protocols also increased with increasing anisotropy. CONCLUSION: For ROI analyses, different NDGDs lead to similar values of FA and D but different eigenvalues. However, different NDGDs at the voxel level provide varying values. The selection of the NDGD, therefore, should depend on the focus of different DTI applications.     

Diffusion tensor imaging of the auditory pathway in sensorineural hearing loss: changes in radial diffusivity and diffusion anisotropy

PURPOSE: To prospectively compare diffusion tensor imaging (DTI) measures of axial diffusivity (lambda parallel), radial diffusivity (lambda perpendicular), mean diffusivity (MD), and fractional anisotropy (FA) along the auditory pathway of patients with sensorineural hearing loss (SNHL) and normal controls. MATERIALS AND METHODS: In 37 individuals with SNHL and 10 healthy controls, two regions of interest (ROIs) positioned along the auditory pathway-the lateral lemniscus (LL) and the inferior colliculus (IC)-were investigated bilaterally using diffusion tensor imaging at 3 T. SNHL patients were divided into three groups: patients with bilateral hearing loss, patients with unilateral hearing loss, and patients with partial hearing loss. DTI measures (lambda parallel, lambda perpendicular, MD, FA) of both ROIs were determined in all subjects. RESULTS: The FA value was reduced and the lambda perpendicular was increased both at the lateral lemniscus and the inferior colliculus of patients with SNHL compared with controls. Similar changes were seen between the ipsilateral and contralateral LL and IC for patients of unilateral profound hearing loss. No changes were observed in any other parameters. CONCLUSION: In SNHL patients DTI showed a high radial diffusivity that consequently led to a decreased fractional anisotropy in the LL and the IC.     

Using diffusion tensor imaging and immunofluorescent assay to evaluate the pathology of multiple sclerosis

Purpose:

To determine the ability of the principal diffusion tensor imaging (DTI) indices to predict the underlying histopathology evaluated with immunofluorescent assay (IFA).

Materials and Methods:

Conventional T2 and 3D multishot‐diffusion weighted echoplanar imaging (3D ms‐DWEPI) was performed on a fixed, ex vivo human cervical spinal cord (CSC) from a patient with a history of multiple sclerosis (MS). In all, 170 regions of interest (ROIs) were selected within the white matter and categorized as a high intensity lesion (HIL), low intensity lesion (LIL), and normal‐appearing white matter (NAWM). The longitudinal diffusivity (λl), radial diffusivity (λr), and fractional anisotropy (FA) were obtained from each ROI. The underlying histopathology was then evaluated using immunofluorescent assay with antibodies directed to myelin and neurofilament staining.

Results:

The mean values for λl and λr were significantly elevated within HIL relative to NAWM and LIL. IFA analysis of HIL demonstrated significant demyelination, without significant if any axon loss. The FA values were significantly reduced in HIL and LILs. FA values were also reduced in lesions with increased λl and λr values relative to normal.

Conclusion:

Aberrant λl, λr, and FA relative to normal values are strong indicators of demyelination. DTI indices are not specific for axon loss. IFA analysis is a reliable method to demonstrate myelin and axon pathology within the ex vivo setting. J. Magn. Reson. Imaging 2011;33:557–564. © 2011 Wiley‐Liss, Inc.     

In vivo diffusion tensor imaging of the human calf muscle

PURPOSE: To demonstrate the feasibility of in vivo calf muscle fiber tracking in human subjects. MATERIALS AND METHODS: An EPI-based diffusion tensor imaging (DTI) sequence with six-direction diffusion gradient sensitization was implemented, and DT images were acquired at 3 Tesla on five subjects using an extremity coil. The mean diffusivity, fractional anisotropy (FA), and fiber angle (with respect to the magnet z-axis) were measured in different muscles, and fibers were tracked from several regions of interest (ROIs). RESULTS: The fiber orientations in the current DTI studies agree well with those determined in previous spectroscopic studies. The orientation angles ranged from 13.4 degrees in the lateral gastrocnemius to 48.5 degrees in the medial soleus. The diffusion ellipsoid in muscle tissue is anisotropic and approximates a prolate model, as shown by color maps of the anisotropy. Fibers were tracked from the different muscle regions, and the unipennate and bipennate structure of muscle fibers was visualized. CONCLUSION: The study clearly shows that in vivo fiber tracking of muscle fibers is feasible and could potentially be applied to study muscle structure function relationships.     

Quantitative magnetic resonance of postmortem multiple sclerosis brain before and after fixation.

Unfixed and fixed postmortem multiple sclerosis (MS) brain is being used to probe pathology underlying quantitative MR (qMR) changes. Effects of fixation on qMR indices in MS brain are unknown. In 15 postmortem MS brain slices T(1), T(2), MT ratio (MTR), macromolecular proton fraction (f(B)), fractional anisotropy (FA), and mean, axial, and radial diffusivity (MD, D(ax), and D(rad)) were assessed in white matter (WM) lesions (WML) and normal appearing WM (NAWM) before and after fixation in formalin. Myelin content, axonal count, and gliosis were quantified histologically. Student's t-test and regression were used for analysis. T(1), T(2), MTR, and f(B) obtained in unfixed MS brain were similar to published values obtained in patients with MS in vivo. Following fixation T(1), T(2) (NAWM, WML) and MTR (NAWM) dropped, whereas f(B) (NAWM, WML) increased. Compared to published in vivo data all diffusivity measures were lower in unfixed MS brain, and dropped further following fixation (except for FA). MTR was the best predictor of T(myelin) (inversely related to myelin) in unfixed MS brain (r = -0.83; P < 0.01) whereas postfixation T(2) (r = 0.92; P < 0.01), T(1) (r = 0.89; P < 0.01), and f(B) (r = -0.86; P < 0.01) were superior. All diffusivity measures (except for D(ax) in unfixed tissue) were predictors of myelin content.     

Measurement of cytotoxic and interstitial components of cerebral edema in acute hepatic failure by diffusion tensor imaging

PURPOSE: To use diffusion tensor imaging (DTI) metrics for measuring cytotoxic and interstitial components of cerebral edema (CE) in acute hepatic failure (AHF) patients. CE is a major complication in patients with AHF. MATERIALS AND METHODS: DTI was performed in 20 patients with AHF and 15 controls. Ten patients underwent repeat imaging after recovery from encephalopathy. Various regions of interest (ROIs) were drawn in the white and deep gray matter of the brain for the quantitation of fractional anisotropy (FA), mean diffusivity (MD), spherical isotropy (CS), linear anisotropy (CL), and planar anisotropy (CP) values. RESULTS: Significantly decreased MD values were observed in most brain ROIs in patients compared to controls. Significantly decreased FA, CL with increased CS values was also observed. In survivors with normal clinical profile after 3 weeks, a significant increase in MD and FA values were associated with decreased CS values in some regions compared to baseline study; however, it was still significantly changed compared to controls. CONCLUSION: Decreased MD and increased CS associated with decreased FA represent cytotoxic and interstitial components of CE, respectively. Incomplete normalization of these metrics in survivors after 3 weeks clinical recovery may be due to incomplete metabolic recovery.     

Diffusion tensor imaging of in vivo and excised rat spinal cord at 7 T with an icosahedral encoding scheme.

Regional values of fractional anisotropy (FA) and mean diffusivity (D(av)) of in vivo and excised rat spinal cords were measured using an iscosahedral encoding scheme that is based on 21 uniformly distributed and alternating gradient directions with an echo planar imaging (EPI) readout. Based on the water phantom studies, this scheme was shown to provide unbiased estimation of FA. The stability of the scanner during the acquisition of diffusion tensor imaging (DTI) data was evaluated. Repeated measurements of the FA values demonstrated excellent reproducibility, as assessed by the Bland-Altman analysis. These studies demonstrated a reduced anisotropy in excised samples relative to in vivo cords. Diffusion in the spinal cord gray matter was shown to be anisotropic. The FA value in the dorsal white matter (WM) was found to be higher relative to the ventral WM. Results from these studies should provide the necessary baseline data for serial in vivo DTI of injured spinal cord.     

Diffusion anisotropy in subcortical white matter and cortical gray matter: changes with aging and the role of CSF-suppression

PURPOSE: To determine the relevance of cerebrospinal fluid (CSF)-suppression for the measurement of diffusion anisotropy in well-localized areas of the brain, particularly the subcortical white matter (WM) within the gyri and cortical gray matter (GM), in young and elderly subjects, and to assess the changes of water diffusivity in the brain with normal aging. MATERIALS AND METHODS: Quantitative measures of anisotropy in 26 regions, including subcortical WM (i.e., in the gyri), cortical GM, major deep WM, and deep GM regions of young (21-25 years, N = 8) and elderly (61-74 years, N = 10) normal volunteers, were assessed with CSF-suppressed diffusion tensor imaging (DTI) relative to standard DTI. RESULTS: CSF-suppressed DTI demonstrated significant increases in fractional anisotropy (FA) of 3-12% in the young and 2-14% in the elderly groups with the largest changes being in the subcortical WM of the gyri. Furthermore, FA decreased by 10-19% in the subcortical WM of the gyri of the elderly subjects relative to the young, primarily due to increases in the perpendicular diffusivity, lambda(3), with age. CONCLUSION: CSF-suppressed DTI yields more accurate measures of quantitative anisotropy in cortical and subcortical brain regions. Reductions of anisotropy with aging were predominantly observed in subcortical WM of the gyri.     

In vivo and ex vivo diffusion tensor imaging of cuprizone‐induced demyelination in the mouse corpus callosum

Diffusion tensor imaging has been widely used in studying rodent models of white matter diseases. In this study, we examined the differences between in vivo and ex vivo fractional anisotropy and diffusivity measurements in the mouse cuprizone model. In the control mouse corpus callosum, ex vivo diffusivities were significantly lower than in vivo measurements, but ex vivo fractional anisotropy values were not significantly different from in vivo fractional anisotropy values. With cuprizone induced demyelination and accompanying pathology in the corpus callosum, changes in in vivo and ex vivo fractional anisotropy and diffusivity measurements were not always in agreement. Our results suggest that ex vivo λ_? was a more reliable indicator of white matter demyelination than in vivo λ_? and in vivo λ_‖ was a more reliable indicator of axonal injury than ex vivo λ_‖ in this model. When comparing in vivo and ex vivo diffusion tensor imaging results of axon and myelin pathology in the rodent models, potential changes in tissue microstructures associated with perfusion fixation should be considered. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.     

In vivo diffusion tensor imaging of the rat spinal cord at 9.4T

PURPOSE: To determine differences in diffusion measurements in white matter (WM) and gray matter (GM) regions of the rat cervical, thoracic, and cauda equina spinal cord using in vivo diffusion tensor imaging (DTI) with a 9.4T MR scanner. MATERIALS AND METHODS: DTI was performed on seven rats in three slices at the cervical, thoracic, and cauda equina regions of the spinal cord using a 9.4T magnet. Axial diffusion weighted images (DWIs) were collected at a b-value of 1000 seconds/mm(2) in six directions. Regions of interest were identified via T2-weighted images for the lateral, dorsal, and ventral funiculi, along with GM regions. RESULTS: Analysis of variance (ANOVA) results indicated significant differences between every WM funiculus compared to GM for longitudinal apparent diffusion coefficient (lADC), transverse apparent diffusion coefficient (tADC), fractional anisotropy (FA), measured longitudinal anisotropy (MA1), and anisotropy index (AI). A significant difference in mean diffusivity (MD) between regions of the spinal cord was not found. Diffusion measurements were significantly different at each spinal level. In general, GM regions were significantly different than WM regions; however, there were few significant differences between individual WM regions. CONCLUSION: In vivo DTI of the rat spinal cord at 9.4T appears sensitive to the architecture of neural structures in the rat spinal cord and may be a useful tool in studying trauma and pathologies in the spinal cord.     

Toward a quantitative assessment of diffusion anisotropy

Indices of diffusion anisotropy calculated from diffusion coefficients acquired in two or three perpendicular directions are rotationally variant. In living monkey brain, these indices severely underestimate the degree of diffusion anisotropy. New indices calculated from the entire diffusion tensor are rotationally invariant (RI). They show that anisotropy is highly variable in different white matter regions depending on the degree of coherence of fiber tract directions. In structures with a regular, parallel fiber arrangement, water diffusivity in the direction parallel to the fibers (D_| ≈ 1400–1800 × 10⁻⁶ mm²/s) is almost 10 times higher than the average diffusivity in directions perpendicular to them ((D + D⊥′)/2 ≈ 150–300 × 10⁻⁶ mm²/s), and is almost three times higher than previously reported. In structures where the fiber pattern is less coherent (e.g., where fiber bundles merge), diffusion anisotropy is significantly reduced. However, RI anisotropy indices are still susceptible to noise contamination. Monte Carlo simulations show that these indices are statistically biased, particularly those requiring sorting of the eigenvalues of the diffusion tensor based on their magnitude. A new intervoxel anisotropy index is proposed that locally averages inner products between diffusion tensors in neighboring voxels. This “lattice” RI index has an acceptably low error variance and is less susceptible to bias than any other RI anisotropy index proposed to date.     

急性期放射性脑损伤磁共振扩散张量成像的定量研究

目的 利用磁共振扩散张量成像(DTI)定量分析,探讨正常脑组织不同部位急性期放射损伤的敏感性。方法 44例欲行全颅放疗的颅内肿瘤患者,在放疗前及放疗后3周行磁共振常规扫描、增强扫描及扩散张量成像,测量非肿瘤侧大脑半球接受总放射剂量为27 Gy时的等剂量区域内脑回灰质、脑回白质、深部灰质、深部白质的表观扩散系数(ADC)、部分各向异性(FA)、相对各向异性(RA)、容积比率(VR)等指标,并进行对比分析。 结果 所有患者常规及增强磁共振扫描非肿瘤侧大脑半球均未发现异常信号,而放疗后脑回灰质ADC值升高(t=-3.819,P<0.05),脑深部灰质核团ADC、容积比率值升高(t=-3.31、-2.810,P<0.05),脑深部灰质核团FA、RA值降低(t=2.906、2.349,P<0.05),其余部位放疗前后DTI各指标差异无统计学意义。结论 在急性期脑灰质较白质对放疗损伤敏感,DTI能从组织细胞功能水平对放射性脑损伤急性反应进行评价。     

正常成人脑结构的弥散张量成像参数测定及分析

目的　运用弥散张量成像 (DTI)方法来探讨脑内不同组织及解剖部位的弥散各向异性特点。资料与方法　采用单次激发自旋回波EPI成像序列 ,将弥散敏感梯度依次施加在六个不同 (P、M、S、MP、PS、MS)的方向进行DTI,获得正常成人脑的弥散张量图及各向异性指数图 ,在脑内不同解剖部位进行各向异性指数、张量的轨迹及平均弥散率测定并进行统计学分析。结果　脑内不同组织及解剖部位的弥散各向异性程度不同 ,脑白质的弥散各向异性远大于丘脑与脑灰质 (P <0 .0 1) ;在脑白质的不同解剖部位 ,其各向异性特点也不相同 (P <0 .0 5 ) ,脑白质连合纤维 (胼胝体 )的各向异性程度最高 ,其次为脑白质的投射纤维 (内囊 ) ,再次为联合纤维 (半卵圆中心 )。张量的轨迹及平均弥散率在脑内的不同部位具有一致性。结论　DTI可准确测定脑内不同组织弥散的各向异性特点 ,并且可清晰显示脑内神经纤维束的方向及走行 ,可为临床脑白质病的研究提供新的功能测定方法     

Conventional DTI vs. slow and fast diffusion tensors in cat visual cortex.

Diffusion tensor imaging (DTI) uses water diffusion anisotropy in axonal fibers to provide a tool for analyzing and tracking those fibers in brain white matter. In the present work, multidirectional diffusion MRI data were collected from a cat brain and decomposed into slow and fast diffusion tensors and directly compared with conventional DTI data from the same imaging slice. The fractional anisotropy of the slow diffusing component (D(slow)) was significantly higher than the anisotropy measured by conventional DTI while reflecting a similar directionality and appeared to account for most of the anisotropy observed in gray matter, where the fiber density is notoriously low. Preliminary results of fiber tracking based on the slow diffusion component are shown. Fibers generated based on the slow diffusion component appear to follow the vertical fibers in gray matter. D(slow)TI may provide a way for increasing the sensitivity to anisotropic structures in cortical gray matter.     

Retrospective measurement of the diffusion tensor eigenvalues from diffusion anisotropy and mean diffusivity in DTI.

A simple theoretical framework to compute the eigenvalues of a cylindrically symmetric prolate diffusion tensor (D) from one of the rotationally-invariant diffusion anisotropy indices and average diffusivity is presented and validated. Cylindrical or axial symmetry assumes a prolate ellipsoid shape (lambdaparallel=lambda1>lambdaperpendicular=(lambda2+lambda3)/2; lambda2=lambda3). A prolate ellipsoid with such symmetry is largely satisfied in a number of white matter (WM) structures, such as the spinal cord, corpus callosum, internal capsule, and corticospinal tract. The theoretical model presented is validated using in vivo DTI measurements of rat spinal cord and human brain, where eigenvalues were calculated from both the set of diffusion coefficients and a tensor analysis. This method was used to retrospectively analyze literature data that reported tensor-derived average diffusivity, anisotropy, and eigenvalues, and similar eigenvalue measurements were obtained. The method provides a means to retrospectively reanalyze literature data that do not report eigenvalues. Other potential applications of this method are also discussed.     

Diffusion tensor mode in imaging of intracranial epidermoid cysts: one step ahead of fractional anisotropy

INTRODUCTION: The signal characteristics of an epidermoid on T2-weighted imaging have been attributed to the presence of increased water content within the tumor. In this study, we explore the utility of diffusion tensor imaging (DTI) and diffusion tensor metrics (DTM) in knowing the microstructural anatomy of epidermoid cysts. MATERIALS AND METHODS: DTI was performed in ten patients with epidermoid cysts. Directionally averaged mean diffusivity (D (av)), exponential diffusion, and DTM-like fractional anisotropy (FA), diffusion tensor mode (mode), linear (CL), planar (CP), and spherical (CS) anisotropy were measured from the tumor as well as from the normal-looking white matter. RESULTS: Epidermoid cysts showed high FA. However, D (av) and exponential diffusion values did not show any restriction of diffusion. Diffusion tensor mode values were near -1, and CP values were high within the tumor. This suggested preferential diffusion of water molecules along a two-dimensional geometry (plane) in epidermoid cysts, which could be attributed to the parallel-layered arrangement of keratin filaments and flakes within these tumors. CONCLUSION: Thus, advanced imaging modalities like DTI with DTM can provide information regarding the microstructural anatomy of the epidermoid cysts.     

Study of the effect of CSF suppression on white matter diffusion anisotropy mapping of healthy human brain.

Healthy human brain diffusion anisotropy maps derived from standard spin echo diffusion tensor imaging (DTI) were compared with those using fluid-attenuated inversion recovery (FLAIR) preparation prior to DTI to null the signal from cerebrospinal fluid (CSF). Consistent comparisons entailed development of DTI postprocessing methods, image masking based on fitting quality, and an objective region-of-interest-based method for assessment of white matter extent. FLAIR DTI achieved an extended delineation of major white-matter tracts (genu, splenium, and body of the corpus callosum) close to large CSF-filled spaces (lateral ventricles), but did not affect representation of tracts remote from CSF (internal and external capsules and coronal radiation). This result, which was detectable qualitatively (visual inspection), was verified quantitatively by analyses of the relative anisotropy (RA) distribution over white matter structures for 11 subjects. FLAIR DTI thus suppresses the CSF signal that otherwise masks underlying anisotropic parenchymal tissue through partial volume averaging.     

Gray and white matter delineation in the human spinal cord using diffusion tensor imaging and fuzzy logic

RATIONALE AND OBJECTIVES: Diffusion tensor imaging (DTI) has been used extensively in determining morphology and connectivity of the brain; however, similar analysis in the spinal cord has proven difficult. The objective of this study was to improve the delineation of gray and white matter in the spinal cord by applying signal processing techniques to the eigenvalues of the diffusion tensor. Our approach involved creating anisotropy indices based on the difference between eigenvalues and mean diffusivity then using a fuzzy inference system (FIS) to delineate between gray and white matter in the human cervical spinal cord. MATERIALS AND METHODS: DTI was performed on the cervical spinal cord in five neurologically intact subjects. Distributions were extracted for regions of gray and white matter through the use of a digitized histologic template. Fuzzy membership functions were created based on these distributions. Detectability index and receiver operating characteristic (ROC) analysis was performed on traditional DTI indices and FIS classified regions. RESULTS: A significantly higher contrast between gray and white matter was observed using fuzzy classification compared with traditionally used DTI indices based on the detectability index (P < .001) and trends in the ROC analysis. Reconstructed images from the FIS qualitatively showed a better anatomical representation of the spinal cord compared with traditionally used DTI indices. CONCLUSIONS: Diffusion tensor imaging using an FIS for tissue classification provides high contrast between spinal gray and white matter compared with traditional DTI indices and may provide a noninvasive technique to quantify the integrity and morphology of the human spinal cord following injury.