Diffusion Weighted Imaging In MS

Background And Purpose
Persistently HypoIntense lesions on T₁-weighted MR images have been shown to correlate with the amount of Axonal damage and clinical disability in Multiple Sclerosis (MS) patients.

The purpose of this study was to investigate whether Diffusion Coefficient (Dav) and Fractional Anisotropy (FA) are able to detect quantifiable differences among three groups of focal NonActive Multiple Sclerosis (MS) lesions that appear qualitatively different on T₁-weighted images.

Methods
Conventional and Diffusion Tensor MR images of the Brain were obtained in 18 patients with Relapsing/Remitting (n = 10) or Secondary/Progressive (n=8) MS and in 18 healthy volunteers.

Focal nonactive MS lesions were classified as T₁ IsoIntense, T₁ mildly HypoIntense, and T₁ severely HypoIntense on unenhanced T₁-weighted images.

Differences among groups were assessed with one-way analysis of variance using the T₁ lesion appearance as the grouping factor and either FA or Diffusion Coefficient (Dav) as the dependent measure.

Results
FA was lowest and Coefficient (Dav) was highest in T₁ severely HypoIntense lesions, and then, in ascending and descending order, respectively, T₁ mildly HypoIntense lesions and T₁ IsoIntense lesions.

A significant difference in the values of FA was detected only between T₁ IsoIntense lesions and T₁ severely HypoIntense lesions (P < .01), whereas no difference was found between T₁ mildly HypoIntense lesions and either one of these two groups.

A significant difference was found in the values of Diffusion Coefficient (Dav) among all investigated lesion groups.

Diffusion Coefficient (Dav) was found to correlate inversely with the T₁-weighted contrast ratio (r=-0.58, P < .0001).

Whereas, FA and Delta FA (percentage of FA variation in the lesion, a relative FA measure that minimizes the effect of FA spatial dependence) were not.

Conclusion
Diffusion Coefficient (Dav) is more sensitive than FA to variations in the degree of T₁ HypoIntensity and, thus, in the amount of the permanent Brain tissue damage in patients with MS.

Background
Current Magnetic Resonance Imaging (MRI) outcome measures such as T₂ lesion load correlate poorly with disability in Multiple Sclerosis.

Diffusion Tensor Imaging (DTI) of the Brain can provide unique information regarding the orientation and integrity of White Matter Tracts in vivo.

Objective
To use this information to map the Pyramidal Tracts of patients with Multiple Sclerosis, investigate the relation between burden of disease in the Tracts and Disability, and compare this with more global Magnetic Resonance estimates of disease burden.

Methods
25 patients with Relapsing/Remitting Multiple Sclerosis and 17 healthy volunteers were studied with DTI.

An algorithm was used that automatically produced anatomically plausible maps of White Matter Tracts.

The integrity of the Pyramidal Tracts was assessed using relative Anisotropy and a novel measure (L(t)) derived from the compounded relative Anisotropy along the Tracts.

The methods were compared with both traditional and more recent techniques for measuring disease burden in Multiple Sclerosis (T₂ lesion load and "Whole Brain" Diffusion Histograms).

Results
Relative Anisotropy and L(t) were significantly lower in patients than controls (p < 0.05).

Pyramidal Tract L(t) in the patients correlated significantly with both Expanded Disability Status Scale (r = -0.48, p < 0.05), and to a greater degree, the Kurtzke Functional System score (KFS-p) (r = -0.75, p < 0.0001).

T₂ lesion load and Diffusion Histogram parameters did not correlate with disability.

Conclusions
Tract mapping using DTI is feasible and may increase the specificity of MRI in Multiple Sclerosis by matching appropriate Tracts with specific clinical scoring systems.

These techniques may be applicable to a wide range of Neurological conditions.

Although quantitative Magnetic Resonance (MR) studies have shown that Primary/Progressive Multiple Sclerosis (PPMS) patients have subtle and diffuse changes of the Normal-Appearing Brain Tissue (NABT), the nature of these changes is still poorly understood.

The aim of this study was to improve our understanding of the NABT damage in PPMS patients.

By comparing Diffusion Tensor Magnetic Resonance (DT MR) quantities of a large portion of the Brain from these patients with those from healthy subjects with and without T₂-visible lesions.

Dual-Echo and DT MR images of the Brain were obtained from 20 patients with PPMS, 20 age- and gender-matched healthy volunteers with normal conventional MR scans of the Brain, and 20 age-, gender- and T₂ lesion volume-matched healthy subjects.

Mean Diffusivity (MD) and Fractional Anisotropy (FA) Histograms of the NABT were derived from all the individuals. Average lesion MD and FA were calculated in PPMS patients and healthy controls with T₂-visible lesions.

MD and FA Histograms-derived metrics of the NABT from PPMS patients differed significantly from the corresponding quantities from healthy volunteers with no Brain T₂-visible lesions.

And from those from healthy volunteers with overt Brain MR abnormalities (p values ranging from < 0.0001 to 0.01).

Average lesion MD was also significantly higher in PPMS patients than in healthy volunteers with T₂-visible lesions (p = 0.03).

In PPMS patients, no significant correlation was found between any of the DT MR quantities of NABT damage and a) the T₂ lesion volume, b) the average lesion MD, and c) the normalized Brain Volume.

This study shows that in PPMS patients there is a significant microscopic damage of the NABT which is independent of the extent of T₂-visible abnormalities.

This suggests that Wallerian Degeneration of Fibers passing through macroscopic abnormalities is not a major factor contributing to diffuse NABT pathology of these patients.

Background And Purpose
Increasing evidence exists that Cerebral Gray Matter (GM) from patients with Multiple Sclerosis (MS) is not spared.

This study was performed to quantify in vivo the extent of Cerebral GM pathologic abnormality in patients with Relapsing/Remitting (RR), Secondary/Progressive (SP), and Primary/Progressive MS, by using Diffusion Tensor (DT) MR imaging.

Methods
Dual-Echo and DT MR imaging of the Brain were performed in 102 patients with MS and 30 healthy volunteers.

After GM segmentation using a technique based on Diffusion Anisotropy thresholding, average Diffusivity () Histograms of the Cerebral GM were produced for all participants.

Results
All Histogram-derived metrics of the GM were significantly different between control volunteers and the whole MS population.

No significant difference was found for any of the Histogram-derived metrics between control volunteers and patients with RRMS.

Whereas significant differences were found for and Histogram peak location between control volunteers and patients with PPMS.

All the Histogram-derived metrics differed significantly between patients with RRMS and patients with SPMS.

Patients with SPMS also had significantly lower than did patients with PPMS.

All Histogram-derived metrics of the GM were strongly correlated with the T₂ lesion volume.

Conclusions
This study confirms the presence of Brain GM changes in patients with MS. It also shows that the extent of such changes is greater during the Progressive forms of the disease.

BiExponential T₂ relaxation of the localized water signal can be used for segmentation of Spectroscopic volumes.

To assess the specificity of the components an iterative relaxation measurement of the localized water signal.

(STEAM, 12 Echo times, geometric spacing from 30 ms to 2000 ms) was combined with Magnetization Transfer (MT) saturation.

40 single Lobe pulses, 12 ms duration, 1440 degrees nominal flip angle, 1 kHz offset, repeated every 30 ms.

Voxels (volume elements) including CSF were examined in Parietal Cortex and PeriVentricular Parietal White Matter (10 each).

As well as 13 voxels in Central White Matter and 16 T₁-HypoIntense Non-Enhancing Multiple Sclerosis lesions without CSF inclusion.

BiExponential models (excluding Myelin water) were fitted to the relaxation data. In PeriVentricular VOIs the component of long T₂ (1736 +/- 168 ms) that is attributed to CSF was not affected by MT.

In Cortical VOIs this component had markedly shorter T₂'s (961 +/- 239 ms) and showed both attenuation and prolongation with MT, indicating contributions from tissue.

MS lesions and Central WM showed a second tissue component of intermediate T₂ (160-410 ms).

In MS lesions, however, markedly less MT of the intermediate component was found, which is consistent with decreased cellularity and exchange in a region that is large compared to Diffusion motion.

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 InterVoxel 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.

In patients with Primary/Progressive Multiple Sclerosis (PPMS), we investigated whether Brain and Cervical Cord structural changes in lesions and Normal-Appearing Brain Tissue (NABT).

Measured using Conventional, Magnetization Transfer (MT), and Diffusion Tensor (DT) MRI, are correlated with movement-associated Cortical activations measured using Functional Magnetic Resonance Imaging (fMRI).

From 26 right-handed PPMS patients and 15 right-handed, sex- and age-matched healthy controls, we obtained:

1. Brain and Cervical Cord Dual-Echo scans and MT Ratio (MTR) maps
2. Brain Mean Diffusivity () maps
3. fMRI (flexion-extension of the last four fingers of the right hand)

All PPMS patients had no previous symptoms affecting their right upper limbs, which were functionally normal. Healthy volunteers showed more significant activation in the Ipsilateral Cerebellar Hemisphere than PPMS patients.

PPMS patients showed greater activation BiLaterally in the Superior Temporal Gyrus, IpsiLaterally in the Middle Frontal Gyrus, and, ContraLaterally in the Insula/Claustrum.

In PPMS patients, moderate to strong correlations (r values ranging from 0.59 to 0.68) were found between relative activations of Cortical Areas.

Located in a widespread network for Sensory-Motor and MultiModal integration and the severity of structural changes of the NABT (as measured using MT and DT MRI) and the severity of Cervical Cord damage (as measured using MT MRI).

This study shows that the pattern of Cortical activation of PPMS patients is different from that of normal controls even when performing a Motor Task with clinically unaffected limbs.

It also suggests that Cortical reorganization might be able to limit the consequences of MS injury in the Brain and Cervical Cord.

(c)2002 Elsevier Science (USA).

The Brains of six healthy volunteers were scanned with a full Tensor Diffusion MRI technique to study the effect of a high b value on Diffusion-Weighted Images (DWIs). The b values ranged from 500 to 5000 s/mm(2).

IsoTropic DWIs, Trace Apparent Diffusion Coefficient (ADC) maps, and Fractional Anisotropy (FA) maps were created for each b value. As the b value increased, ADC decreased in both the Gray and White Matter.

Furthermore, ADC of the White Matter became lower than that of the Gray Matter, and, as a result, the White Matter became brighter than the Gray Matter in the IsoTropic DWIs.

Quantitative analysis showed that these changes were due to NonMonoExponential Diffusion signal decay of the Brain tissue, which was more prominent in White Matter than in Gray Matter.

There was no significant change in relation to the b value in the FA maps. High b value appears to have a dissociating effect on Gray and White Matter in DWIs.

New MRI techniques such as the analysis of Magnetization Transfer or Diffusion have provided evidence for subtle progressive alterations in tissue integrity prior to focal leakage of the Blood-Brain Barrier (BBB) as part of Plaque formation in Multiple Sclerosis.

Since inflammation is capable of modulating the MicroCirculation, we investigated the hypothesis that changes in the local perfusion might be one of the earliest signs of lesion development.

20 patients with Definite Relapsing/Remitting Multiple Sclerosis were analyzed with regard to Cerebral blood volume, Cerebral blood flow, mean transit time and Apparent Diffusion Coefficient (ADC), as well as conventional MRI parameters, on monthly follow-up scans.

Among 89 Gadolinium-enhancing lesions, we selected 18 that developed during the study and met strict inclusion criteria.

In these, changes of perfusion parameters were detectable not only prior to the BBB breakdown, but also prior to increases in the ADC.

Our data indicate that inflammation is accompanied by altered local perfusion, which can be detected prior to permeability of the BBB.

Diffusion-weighted Magnetic Resonance Imaging is a specialized technique that measures the degree of Diffusion of water molecules within ExtraCellular Space and between IntraCellular and ExtraCellular space.

Diffusion-weighted imaging signal is high (bright) when Diffusion is restricted, as occurs in CytoToxic damage from Ischemia, Inflammation, Trauma, or Tumor.

This technique, now available on most Magnetic Resonance Imaging units, is especially helpful in detecting early Ischemic Stroke and Multiple Sclerosis and in differentiating Arachnoid Cyst from Epidermoid Tumor and Brain Abscess from Neoplasm.

Quantitative Diffusion-weighted MRI has been applied to the study of Neurological Diseases, including Multiple Sclerosis, where the Molecular Self-Diffusion Coefficient D has been measured in both lesions and Normal-Appearing White Matter.

Histograms of D have been used as a novel measure of the "lesion load", with potential applications that include the monitoring of efficacy in new treatment trials.

However different ways of measuring D may affect its value, making comparison between different centers and research groups impossible.

We aimed to assess the effect, if any, of using two different MRI sequences on the value of D.

We studied 13 healthy volunteers, using two different quantitative Diffusion sequences (including different b(max) values and gradient applications).

Maps of D were analyzed using both Regions Of Interest (ROI) in White Matter and "whole Brain" Histograms, and compared between the two sequences.

In addition, we studied three standardized test liquids (with known values of D) using both sequences.

Histograms from the two sequences had different distributions, with a greater spread and higher peak position from the sequence with lower b(max). This greater spread of D was also evident in the White Matter and test liquid ROI.

"Limits of agreement" analysis demonstrated that the differences could be clinically relevant, despite significant correlations between the sequences obtained using simple rank methods.

We conclude that different quantitative Diffusion sequences are unlikely to produce directly comparable values of D, particularly if different b(max) values are used.

In addition, the use of inappropriate statistical tests may give false impressions of close agreement.

Standardization of methods for the measurement of D are required if these techniques are to become useful tools, for example in monitoring changes in the disease burden of Multiple Sclerosis.