Mean Mean Diffusivity Values Research Articles

The relationship between cortical lesions and periventricular NAWM abnormalities suggests a shared mechanism of injury in primary-progressive MS.

In subjects with multiple sclerosis (MS), pathology is more frequent near the inner and outer surfaces of the brain. Here, we sought to explore if in subjects with primary progressive MS (PPMS) cortical lesion load is selectively associated with the severity of periventricular normal appearing white matter (NAWM) damage, as assessed with diffusion weighted imaging.To this aim, twenty-four subjects with PPMS and twenty healthy controls were included in the study. Using diffusion data, skeletonized mean diffusivity (MD) NAWM maps were computed excluding WM lesions and a 2 mm-thick peri-lesional rim. The supra-tentorial voxels between 2 and 6 mm of distance from the lateral ventricles were included in the periventricular NAWM mask while the voxels between 6 and 10 mm from the lateral ventricles were included in the deep NAWM mask; mean MD values were then computed separately for these two masks. Lastly, cortical lesions were assessed on phase-sensitive inversion recovery (PSIR) images and cortical thickness was quantified on volumetric T1 images.Our main result was the observation in the PPMS group of a significant correlation between periventricular NAWM MD values and cortical lesion load, with a greater cortical lesion burden being associated with more abnormal periventricular NAWM MD. Conversely, there was no correlation between cortical lesion load and deep NAWM MD values or periventricular WM lesions.Our data thus suggest that a common – and relatively selective - factor plays a role in the development of both cortical lesion and periventricular NAWM abnormalities in PPMS.

Abstract WP43: Advanced White Matter Disease is Associated With Increased Blood-Brain Barrier Permeability and Early Diffuse Microstructural Changes in Patients With Acute Ischemic Stroke

Background: In acute ischemic stroke (AIS), cerebral tissue damage and clinical outcomes are linked to pre-existing microvascular dysfunction, manifesting as white matter hyperintensity (WMH). Elevated blood-brain barrier permeability (BBB-P) has been implicated in advanced WMH. We tested the microstructural integrity of BBB as measured by dynamic susceptibility contrast (DSC) MRI K 2 coefficient values in AIS patients with advanced WMH. Methods: Twenty patients enrolled in a prospective acute MRI study underwent diffusion tensor (DTI) and DSC MRI on admission for AIS. BBB-P estimates were derived from DSC MRI using the K 2 coefficients. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) maps were calculated. Mean K 2 , MD, AD, RD and FA values were measured in regions of WMH and normally appearing white matter (NAWM) in the hemisphere contralateral to AIS and compared (two-tailed Student t-Test). WMH volume (WMHv) was assessed on acute FLAIR using a validated semi-automated volumetric protocol. Linear regression was performed to evaluate significant predictors of K 2 , MD, AD, RD, and FA. Correlation analysis was performed (Pearson product-moment). Results: Mean age of subjects was 66 (±10) years, 30% were women, median WMHv 3.5cm 3 [IQR 1.6-7.4]. K 2 values differed significantly between WMH and NAWM (0.32 x10 -3 vs. 1.1 x10 -3 , p<0.03), as did the diffusivity metrics for WMH and NAWM (FA: 0.25 vs 0.38; MD: 1.3 x10 -3 vs 0.84 x10 -3 ; AD: 1.6 x10 -3 vs 1.2 x10 -3 ; RD: 1.14 x10 -3 vs 0.66 x10 -3 ; all p<0.0001). K 2 and RD values were correlated within WMH (R=-0.45, P=0.046) but not in NAWM (R=0.06, P=0.81). Multivariate analysis found systolic BP (SBP) and lnWMHv to be significant predictors of MD (P=0.0009), AD (P=0.002), and RD (P=0.002) in NAWM. Discussion: BBB-P and diffusivity values in patients with AIS and advanced leukoaraiosis differed significantly between WMH and NAWM in the hemisphere contralateral to acute infarct. Association between the RD and K 2 coefficients in WMH suggests the role of BBB-P in pathophysiology of WMH and the loss of microstructural white matter integrity associated with it. Further, the influence of SBP and lnWMHv on NAWM diffusivity values suggests ongoing risk for developing future WMH.

Discriminative analysis of early-stage Alzheimer’s disease and normal aging with automatic segmentation technique in subcortical gray matter structures: a multicenter in vivo MRI volumetric and DTI study

Previous studies have revealed that amyloid depositions exist in not only the hippocampus but in other subcortical gray matter structures as well. Diffusion-tensor imaging (DTI) parameters might be more sensitive measures of early degeneration in Alzheimer's disease (AD) than conventional magnetic resonance imaging (MRI) techniques. To evaluate the significance of the volumes and the mean diffusivity (MD) values of subcortical gray matter structures in discrimination between early-stage AD and normal subjects using the Integrated Registration and Segmentation Tool in FMRIB's Software Library. Fifty-three cases of early-stage AD and 30 normal aging volunteers from two hospitals were scanned with 3D-FSPGRIR and SSSE-EPI sequences using two similar 1.5T MR systems. The mean relative volumes and mean MD values of subcortical gray matter structures were compared between early-stage AD and control groups. Binary logistic regression analysis and receiver-operating characteristic (ROC) curves were applied to assess the diagnostic significance of every structure's relative volume, MD value, and combination of both. The relative volumes of the left hippocampus, right amygdala, bilateral thalamus, right caudate, left putamen, and bilateral pallidum were significantly lower in the early-stage AD group than in the control group (P < 0.05). The MD values of the bilateral hippocampus and pallidum, and of the right thalamus and caudate were significantly elevated in the early-stage AD group (P < 0.05). In binary logistic regression analysis, the relative volume of left hippocampus and age entered the final model of volumetric analysis. The MD values of bilateral hippocampi and pallidums entered the final model of MD analysis. The MD values of bilateral hippocampi and pallidums, and the relative volume of left pallidum, entered the final model of combination analysis. The accuracy of three models was 84.7%, 88.9%, and 93.1%, respectively. Pathological changes takes place in the hippocampus and other subcortical gray matter structures in early-stage AD. Diffusive imaging has great diagnostic significance in early-stage AD. The combination of both imaging modalities can lead to better discrimination between early-stage AD and normal aging.

Clinical relevance of diffusion tensor imaging parameters in lumbar disco-radicular conflict

To measure the fractional anisotropy (FA) and the mean diffusivity (MD) values of L4, L5 and S1 nerve roots using diffusion tensor imaging (DTI) and to correlate them with four different clinical patterns. Fifty-six human participants were prospectively included and divided between four groups: healthy subjects, patients with clinical symptomatic nerve root pain with and without anatomical discoradicular conflict and patients with incidental anatomical discoradicular conflict seen on magnetic resonance imaging (MRI). MRI protocol included anatomical sequences (sagittal T1- and T2-weighted, axial T2-weighted) and a 25 directions DTI sequence. FA and MD values were measured in consensus by two readers and compared between the four groups. Mean FA and MD values were significantly different for patients with clinically symptomatic nerve root pain (n=27) both with (n=16) (FA=0.187±0.015; MD=510±40) and without (n=11) (FA=0.193±0.011; MD=490±30.5) anatomical discoradicular conflict compared to healthy subjects (n=29) (FA=0.221±0.011; MD=460.9±35.5) including 2 subjects with incidental anatomical discoradicular conflict (FA=0.211±0.013; MD=450.8±41.2) on MRI (P=0.003). Measurement of FA and MD values of L4, L5 and S1 nerve roots using DTI could be useful in lumbar nerve root pain assessment. Further studies with different image processing methods are needed.

Age-related Changes of White Matter in the Elderly Population Measured by Diffusion Tensor Imaging

Background: A decline in cerebral White Matter (WM) integrity occurs across the adult lifespan, with more rapid degradation later in life. Diffusion Tensor Imaging (DTI) is a non-invasive method to evaluate the microscopic changes of WM in vivo. Linear regression models have been applied to depict the relationship between diffusion properties, such as Fractional Anisotropy (FA) and Mean Diffusivity (MD), derived from DTI and age. However, the fit of these linear regression models is unsatisfactory. Objectives: The purpose of our study was to investigate the age-related changes of WM in an elderly population. Methods: We performed statistical parametric mapping with DTI to evaluate the patterns of age-related microscopic WM changes with voxel-based analysis in the elderly population (>55 years old). A linear regression model was used to examine the associations between DTI parameters and age. Results: The fit of the linear regression model depicting the association between mean global FA, MD values (FA, MD derived from global WM), and age was better than that reported in prior studies using DTI (R2=0.4252, p<0.001 for global FA and age; R2=0.5309, p<0.001 for global MD and age). Moreover, comparable to previous studies, the mean global FA showed a significant negative correlation with mean global MD, indicating a true age-related phenomenon of increased interstitial or intracellular fluid accumulation in cerebral WM. The mean frontal FA value was significantly lower than the mean global FA value. However, there was no significant difference between the mean frontal MD value and the mean global MD value. Conclusions: Focusing on the elderly population, we can improve the fit of linear regression models to investigate the age-related changes of WM by DTI. These results suggest that age-related microscopic changes of WM might be occurring more consistently in later life.

Technical Note: DTI measurements of fractional anisotropy and mean diffusivity at 1.5 T: Comparison of two radiofrequency head coils with different functional designs and sensitivities

Diffusion tensor imaging (DTI) is highly sensitive to noise and improvement of radiofrequency coil technology represents a straightforward way for augmenting signal-to-noise ratio (SNR) performance in magnetic resonance imaging (MRI) scanners. The aim of this study was to characterize the dependence of DTI measurements of fractional anisotropy (FA) and mean diffusivity (MD) on the choice of head coil, comparing two head coils with different functional designs and sensitivities. Fourteen healthy subjects underwent DTI acquisitions at 1.5 T. Every subject was scanned twice, using a standard quadrature birdcage head coil (coil-A) and an eight-channel array head coil (coil-B). FA and MD maps, estimated using both the linear least squares (LLS) and nonlinear least squares (NLLS) methods, were nonlinearly normalized into a standard space. Then, volumetric regions of interest encompassing typical white and gray matter structures [splenium of the corpus callosum (SCC), internal capsule (IC), cerebral peduncles (CP), middle cerebellar peduncles (MCP), globus pallidus (GP), thalamus (TH), caudate (CA), and putamen (PU)] were analyzed. Significant differences and trends of variation in DTI measurements were assessed by the Wilcoxon test for paired samples with and without Bonferroni correction for multiple comparisons, respectively. The overall SNR of coil-B was 30% higher than that of coil-A. When comparing DTI measurements (coil-B versus coil-A), mean FA values (SCC, IC, and TH), mean MD values (IC, CP, GP, and TH), FA standard deviation (CP, MCP, GP, and CA), and MD standard deviation (IC, CP, TH, and PU) resulted decreased (significant difference, p(cor) < 0.05, or trend of variation, P(uncor) < 0.05) in several gray and white matter regions of the human brain. With the exception of CP, the results in terms of revealed significant difference or trend of variation were independent of the method (LLS and NLLS) used for estimating the diffusion tensor. In various gray and white matter structures, the eight-channel array head coil yielded more precise and accurate measurements of DTI derived indices compared to the standard quadrature birdcage head coil.

Optic Nerve and Optic Radiation Neurodegeneration in Patients with Glaucoma: In Vivo Analysis with 3-T Diffusion-Tensor MR Imaging

To evaluate, with high-field-strength diffusion-tensor (DT) magnetic resonance (MR) imaging, the axonal architecture of the optic nerves and optic radiations in patients with glaucoma and determine whether DT MR imaging-derived parameters correlate with disease severity. The study was approved by the institutional review board. All participants provided written informed consent. Sixteen patients with primary open-angle glaucoma were examined. Glaucoma severity was clinically assessed with use of a six-stage system based on static threshold visual field parameters. Ten healthy individuals served as control subjects. DT MR imaging was performed with a 3-T MR unit. Mean diffusivity (MD) and fractional anisotropy (FA) maps were automatically created. Regions of interest were positioned on the MD and FA maps, and mean MD and mean FA values were calculated for each optic nerve and each optic radiation. The optic radiations and optic nerves of patients with glaucoma, as compared with control subjects, had significantly higher MD and significantly lower FA. The mean MD values for the optic nerves and the glaucoma stages varied consistently (r = 0.8087, P < .0001). A negative correlation between mean FA for the optic nerves and glaucoma stage (r = -0.7464, P < .0001) was observed. Glaucoma is a complex neurologic disease that affects optic nerves and optic radiations. The finding that DT MR imaging-derived MD and FA in the optic nerves correlate with glaucoma severity suggests that these parameters could serve as complementary indicators of disease severity.

Retrograde Wallerian degeneration of cranial corticospinal tracts in cervical spinal cord injury patients using diffusion tensor imaging

Diffusion tensor imaging (DTI) has the potential to reveal disruption of white matter microstructure in chronically injured spinal cords. We quantified fractional anisotropy (FA) and mean diffusivity (MD) to demonstrate retrograde Wallerian degeneration (WD) of cranial corticospinal tract (CST) in cervical spinal cord injury (SCI). Twenty-two patients with complete cervical SCI in the chronic stage were studied with DTI along with 13 healthy controls. Mean FA and MD values were computed for midbrain, pons, medulla, posterior limb of internal capsule, and corona radiata. Significant reduction in the mean FA and increase in MD was observed in the cranial CST in patients with SCI compared with controls, suggesting retrograde WD. Statistically significant inverse FA and MD changes were noted in corona radiata, indicating some restoration of spared white matter tracts. Temporal changes in the DTI metrics suggest progressing degeneration in different regions of CST. These spatiotemporal changes in DTI metrics suggest continued WD in injured fibers along with simultaneous reorganization of spared white matter fibers, which may contribute to changing neurological status in chronic SCI patients.

Diffusion-Tensor Imaging for Glioma Grading at 3-T Magnetic Resonance Imaging

To retrospectively determine whether fractional anisotropy (FA) or mean diffusivity (MD) value at 3-T diffusion-tensor imaging is different between low- and high-grade gliomas and may be useful for glioma grading. Review board approval was obtained, and informed consent was waived. Diffusion-tensor imaging was performed in 27 patients with surgically proved gliomas (19 high-grade and 8 low-grade gliomas). Fractional anisotropy and MD values were measured in 3 regions; peritumoral edema, and enhancing and nonenhancing tumor regions. We compared mean FA and MD values of nonenhancing tumor regions between low- and high-grade gliomas and compared the FA and MD values among the 3 mentioned regions in high-grade gliomas. The relationship between FA and MD values of tumors was also investigated. Statistical analysis was performed using the Student t test and Pearson correlation coefficients. In the nonenhancing regions of tumors, FA ratios were not significantly different between low- and high-grade gliomas (0.472 and 0.701, P = 0.075), but MD ratios were significantly lower in high-grade gliomas (1.899 and 1.23, P < 0.001). In high-grade gliomas, enhancing tumors showed a tendency toward a lower FA ratio than nonenhancing tumors (P = 0.034), but FA values or ratios of peritumoral edema were not significantly different from those of enhancing or nonenhancing tumor. No strong relationship was found between FA and MD values. Fractional anisotropy values of low- and high-grade gliomas were not significantly different. However, MD values of nonenhancing low-grade gliomas were significantly higher than those of nonenhancing high-grade gliomas, which will be useful for the grading of nonenhancing infiltrative gliomas.

Diffusion-Tensor MR Imaging of Cortical Lesions in Multiple Sclerosis: Initial Findings

To prospectively perform a direct measurement of fractional anisotropy (FA) and mean diffusivity (MD) in cortical lesions of patients with multiple sclerosis (MS). The study was approved by the institutional review board and was HIPAA compliant; informed consent was obtained. Magnetic resonance (MR) images, including double inversion-recovery (DIR), phase-sensitive inversion-recovery (PSIR), and diffusion-tensor images, were acquired from nine MS patients with cortical lesions (five women, four men; median age, 47 years) and nine age- and sex-matched volunteer control subjects. Following nonlinear elastically constrained image registration for aligning diffusion-weighted images to DIR images, maps of FA and MD were computed for each subject. Cortical lesions were identified on DIR images and validated by using PSIR images. The diffusion-tensor imaging maps were then overlaid on the coregistered DIR images, and mean FA and MD values were measured in regions of interest drawn on the cortical lesions. Differences between normal gray matter (GM) and cortical lesions were evaluated by using the generalized estimating equation. FA and MD histograms of whole brain and GM (global analysis) in healthy control subjects and MS patients were also computed for comparison with those in previously published studies. FA and MD values were significantly higher in cortical lesions compared with similar regions in healthy control subjects. Histogram peak FA was significantly decreased and peak MD was significantly increased in patients relative to control subjects. DIR and PSIR combined with nonlinear image registration allowed direct focal measurement of FA and MD in cortical lesions.

Peritumoral edema of meningiomas and metastatic brain tumors: differences in diffusion characteristics evaluated with diffusion-tensor MR imaging

We prospectively compared the fractional anisotropy (FA) and mean diffusivity (MD) of the peritumoral edema of meningiomas and metastatic brain tumors with diffusion-tensor magnetic resonance (MR) imaging. The study protocol was approved by the local ethics committee, and written informed consent was obtained. Preoperative diffusion-tensor MR imaging was performed in 15 patients with meningiomas and 11 patients with metastatic brain tumors. Regions of interest (ROI) were placed in the peritumoral edema and normal-appearing white matter (NAWM) of the contralateral hemisphere to measure the FA and MD. The FA and MD ratios were calculated for each ROI in relation to the NAWM of the contralateral hemisphere. Changes in peritumoral MD and FA, in terms of primary values and ratios, were compared using a two-sample t-test; P < 0.05 was taken as indicating statistical significance. The mean MD values (x10(-3) mm(2)/s) of the peritumoral edema for metastases and meningiomas, respectively, were 0.902 +/- 0.057 and 0.820 +/- 0.094, the mean MD ratios were 220.3 +/- 22.6 and 193.1 +/- 23.4, the mean FA values were 0.146 +/- 0.026 and 0.199 +/- 0.052, and the mean FA ratios were 32.3 +/- 5.9 and 46.0 +/- 12.1. All the values were significantly different between metastases and meningiomas (MD values P = 0.016, MD ratios P = 0.006, FA values P = 0.005, FA ratios P = 0.002). The peritumoral edema of metastatic brain tumors and meningiomas show different MD and FA on diffusion-tensor MR imaging.

Elevated mean diffusivity in widespread brain regions in congenital central hypoventilation syndrome

To investigate whether mean diffusivity (MD) values are altered in brain areas underlying cardiovascular and respiratory control in congenital central hypoventilation syndrome (CCHS). Conventional and diffusion tensor imaging were performed in 15 CCHS and 30 control subjects, using a 3.0-Tesla MRI unit. Mean diffusivity maps were calculated from diffusion-weighted images, spatially normalized, smoothed, and compared between groups using analysis of covariance at each voxel with age as covariate. Global mean MD values of gray and white matter were determined in individual subjects and compared between groups and with age. Increased MD values appeared in CCHS over control subjects within multiple areas influencing breathing and cardiovascular control, including the midbrain, pons, and dorsal and ventral medulla. Other altered sites included cerebellar cortex and deep nuclei, basal ganglia, basal forebrain, and temporal and frontal cortices. Global mean MD values for gray and white matter did not differ between groups; however, gray matter MD values significantly increased with age (P < 0.02) in CCHS patients only. Increased MD values suggest regional alterations or injury; affected areas include brainstem sites classically associated with autonomic and respiratory control. Other altered regions mediate additional physiological characteristics impaired in CCHS.

Diffusion tensor imaging of cerebral white matter in patients with myotonic dystrophy

To determine whether myotonic dystrophy (MyD) patients have diffusion tensor abnormalities suggestive of microstructural changes in normal-appearing white matter (NAWM). Conventional and diffusion tensor magnetic resonance images of the brain were obtained in 19 MyD patients and 19 age-matched normal control subjects. Fractional anisotropy (FA) and mean diffusivity (MD) values were calculated in white matter lesions (WMLs) and NAWM in MyD patients and in the white matter of normal control subjects. Differences between WML and NAWM values and between MyD patient and control subject values were analyzed statistically. Significantly lower FA and higher MD values were found in all regions of interest in the NAWM of MyD patients than in the white matter of control subjects (P<0.01), as well as significantly lower FA and higher MD values in WMLs than in NAWM of MyD patients (P < 0.05). There was no significant correlation of mean FA or MD values in NAWM with patient age, age at onset, or duration of illness (P>0.1). Diffusion tensor imaging analysis suggests the presence of diffuse microstructural changes in NAWM of MyD patients that may play an important role in the development of disability.