Diffusion Weighted Imaging In MS

Purpose
To prospectively perform a direct measurement of Fractional Anisotropy (FA) and Mean Diffusivity (MD) in Cortical Lesions of patients with Multiple Sclerosis (MS).

Materials And Methods
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.

Results
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.

Conclusion
DIR and PSIR combined with nonlinear image registration allowed direct focal measurement of FA and MD in Cortical Lesions.

(c) RSNA, 2008.

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 T₁, T₂, 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.

T₁, T₂, MTR, and f(B) obtained in unfixed MS Brain were similar to published values obtained in patients with MS in vivo.

Following fixation T₁, T₂ (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 T₂ (r = 0.92; P < 0.01), T₁ (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.

(c) 2008 Wiley-Liss, Inc.

Background And Purpose
Although patients with Tuberous Sclerosis Complex (TSC) manifest various structural abnormalities, we hypothesized that White Matter (WM) structures that appear normal on conventional MR imaging may be accompanied by MicroStructural changes, such as Gliosis and Myelinization defects.

Our objective was to determine in vivo whether there was evidence for WM MicroStructural changes by using Diffusion Tensor Imaging (DTI).

Materials And Methods
We used DTI to evaluate Diffusivity and Anisotropy in Normal-Appearing WM (NAWM) of 6 children with TSC and 12 age-matched control subjects.

The anterior and posterior limbs of the Internal Capsule, the External Capsule, and the Genu and Splenium of the Corpus Callosum were assessed.

We hypothesized that previously reported DTI abnormalities of NAWM in patients with TSC may not be equal in all Diffusion directions as measured by the major, middle, and minor eigenvalues.

Results
When combining NAWM regions in patients with TSC, we observed a significant increase in Mean Diffusivity (P = .003) and a decrease in Anisotropy (P = .03) compared with those of controls.

However, the increase in Diffusivity was more pronounced in directions orthogonal to the Axons measured by the minor and middle eigenvalues (P = .005) than by the major eigenvalue (P = .02).

Conclusion
Our findings revealed a decrease in Anisotropy and an increase in longitudinal and Radial Diffusivities in NAWM beyond the location of TSC lesions seen on conventional MR imaging.

The Axonal MicroStructural changes suggested by our study may be related to changes in Myelin packing due to Giant Cells accompanied by Gliosis and Myelination defects known to occur in TSC WM.

Purpose
To investigate the utility of voxelwise analysis in the detection of lesions in the Normal-Appearing White Matter (NAWM) of individual Multiple Sclerosis (MS) patients.

Materials And Methods
Diffusion Tensor Imaging (DTI) was performed on 10 normal controls and six patients with MS lesions.

The Fractional Anisotropy (FA) maps derived from the Diffusion-weighted images were then spatially normalized (via an affine transformation) into Montreal Neurological Institute (MNI) space.

And, the normalized FA map of each of the patients was compared voxelwise with the normalized FA maps of the group of normals in a one-sample t-test (P = 0.0001).

Two independent board-certified NeuroRadiologists reviewed the data.

Results
In the patient data for all six cases, the two reviewers determined detection sensitivities of 72% and 96% for the voxelwise technique based on known Fluid-Attenuated Inversion-Recovery (FLAIR) lesions.

In addition, between the two reviewers, nine NAWM regions exhibiting FA reductions were identified in the six patients.

However, numerous regions of abnormal FA were detected that were attributed to poor intersubject image registration.

Conclusion
Voxelwise analysis of spatially normalized FA maps has the potential to identify regions of FA reduction in lesions and in the NAWM of individual MS patients in a rapid and reproducible fashion.

J. Magn. Reson. Imaging 2007;26:552-556. (c) 2007 Wiley-Liss, Inc.

Our purpose was to evaluate the ability of Diffusion Tensor Imaging (DTI) to characterize Cervical Spinal Cord White Matter (WM) in patients with Multiple Sclerosis (MS).

DTI were obtained in 21 MS patients and 21 control subjects (CS). Regions Of Interest (ROIs) were placed at C2/3, C3/4, and C4/5 within the right, left, and dorsal (WM) to calculate Fractional Anisotropy (FA) and the Apparent Diffusion Coefficient (ADC).

Measurements in plaques and Normal-Appearing White Matter (NAWM) of MS patients were compared with mean FA and ADC of WM in CS. FA was significantly lower in all regions in MS patients than in CS.

ADC was significantly higher in all regions in MS patients than in CS except for in the dorsal WM at C2/3 and the bilateral WM at C4/5. The mean FA was 0.441 for plaques and 0.542 for NAWM, as compared with 0.739 in CS.

The mean ADC was 0.810 x 10(-3) mm(2)/s for plaques and 0.722 x 10(-3) mm(2)/s for NAWM, as compared with 0.640 x 10(-3) mm(2)/s for CS. FA and ADC showed significant differences between plaques, NAWM and control WM(P < 0.01).

Objective
To study the White Matter of patients with Multiple Sclerosis (MS) with Diffusion Tensor Magnetic Resonance (MR) Imaging (DTI).

Method
Forty patients with clinical-laboratorial diagnosis of Relapsing/Remitting MS and 40 age- and sex-matched controls, who underwent conventional and functional (DTI) MR imaging, were included in the study.

The DTI sequences resulted in maps of Fractional Anisotropy (FA) and Regions Of Interest were placed on the plaques, peri-plaque regions, Normal-Appearing White Matter (NAWM) around the plaques, Contralateral Normal White Matter (CNWM) and normal White Matter of the controls (WMC).

The FA values were compared and the statistical treatment was performed with the Mann-Whitney U test.

Results
The mean FA in plaques was 0.268, in PeriPlaque regions 0.365, in NAWM 0.509, in CNWM 0.552 and in WMC 0.573.

Statistical significant differences in FA values were observed in plaques, peri-plaque regions and in NAWM around the plaques when compared to the White Matter in the control group.

There was no significant difference between the FA values of the CNWM of patients with MS and normal white matter of controls.

Conclusion
Patients with MS show difference in the FA values of the plaques, PeriPlaques and NAWM around the plaques when compared to the normal White Matter of controls.

As a result, DTI may be considered more efficient than conventional MR imaging for the study of patients with MS.

Diffusion Tensor Imaging (DTI) is a promising method for characterizing MicroStructural changes or differences with NeuroPathology and treatment.

The Diffusion Tensor may be used to characterize the magnitude, the degree of Anisotropy, and the orientation of directional Diffusion.

This review addresses the biological mechanisms, acquisition, and analysis of DTI measurements.

The relationships between DTI measures and White Matter pathologic features (e.g., Ischemia, Myelination, Axonal Damage, Inflammation, and Edema) are summarized.

Applications of DTI to tissue characterization in NeuroTherapeutic applications are reviewed.

The interpretations of common DTI measures (Mean Diffusivity, MD; Fractional Anisotropy, FA; Radial Diffusivity, D(r); and Axial Diffusivity, D(a)) are discussed.

In particular, FA is highly sensitive to MicroStructural changes, but not very specific to the type of changes (e.g., Radial or Axial).

To maximize the specificity and better characterize the tissue MicroStructure, future studies should use multiple Diffusion Tensor measures (e.g., MD and FA, or D(a) and D(r)).

There have been several methods proposed so far using Diffusion Tensor Imaging (DTI) for the assessment of Normal-Appearing Brain Tissue (NABT) injury in Multiple Sclerosis (MS).

However, for these methods, the analyses of the NABT injury at the cellular level, wherein histological examinations can be used, still present challenging problems.

We developed a method of segregating NABT into the following anatomical structures using lambda chart analysis associated with a two-dimensional Gaussian deconvolution of Diffusion characteristic functions:

1. Structures primarily composed of small Neurons and Glia;
2. Structures primarily composed of large Neurons;
3. Structures primarily composed of short Axons; and
4. Structures primarily composed of long Axons

Each segregated structure that had a distinctive Diffusion characteristic was subjected to the statistical inference of DTI-derived parameters for 14 patients with conventional Relapsing/Remitting MS (RRMS) and 20 age-matched healthy volunteers.

In all of the structures, the trace values were significantly higher and the Fractional Anisotropy values were significantly lower in the RRMS patients than in the healthy volunteers.

Furthermore, the Volume Fractions of the structures primarily composed of short Axons markedly decreased, whereas those of the structures primarily composed of small Neurons and Glia markedly increased.

These results suggest that Axonal Loss and Glial proliferation predominantly occurred in the SubCortical White Matter and adjacent deep Cortical layer, namely, the JuxtaCortical region.

This cell-oriented analysis of NABT injury using DTI confirmed in vivo the histological observation that the JuxtaCortical region is the most vulnerable site in MS.

Diffusion Tensor Imaging (DTI) measures have shown to be sensitive to White Matter (WM) damage in Multiple Sclerosis (MS), not only inside focal lesions but also in user-defined regions in the so-called Normal-Appearing White Matter (NAWM).

New analysis techniques for DTI measures are now available that allow for hypothesis-free localization of damage.

We performed DTI measurements of 30 MS patients selected for low focal lesion loads, and of 31 age-matched healthy controls and analyzed these using Tract-Based Spatial Statistics (TBSS).

Patients were found to have a lower Fractional Anisotropy (FA) compared to controls in a number of Brain Regions, including the Fornices, the Left Corona Radiata, the Inferior Longitudinal Fasciculus in both Hemispheres, both Optic Radiations, and parts of the Corpus Callosum.

In the regions of reduced FA, an increase in Radial Diffusivity and a less pronounced increase of Axial Diffusivity were found.

NeuroCognitive assessment showed that patients had normal VisuoSpatial Memory performance, just-normal Attention, and Impaired Processing Speed.

The latter was associated with abnormal FA in the Corpus Callosum, an area which was relatively devoid of lesions visible on proton density-weighted images in our patients.

TBSS can be useful in future studies with other MS patient samples to provide an unbiased localization of damage and generate location-specific hypotheses.