M. Cercignani

Diffusion tensor magnetic resonance imaging in multiple sclerosis

Objectives: To quantify, using diffusion tensor imaging (DTI), the tissue damage in lesions and normal-appearing white matter (NAWM) from a large cohort of patients with MS and to investigate the magnitude of the correlation between DTI-derived metrics and clinical disability. Methods: Dual-echo and DTI scans were obtained from 78 patients with relapsing-remitting, secondary progressive, or primary progressive MS and from 20 normal control participants. Post-contrast T1-weighted images were also obtained from the patients. After creating mean diffusivity () and fractional anisotropy (FA) images and image coregistration, and FA values were measured for 4846 lesions (3207 nonenhancing T1-isointense, 1511 nonenhancing T1-hypointense, and 128 enhancing), 497 NAWM areas from patients, and 160 white matter areas from the controls. Results: The average lesion was higher and the average lesion FA was lower than the corresponding quantities of the NAWM (p < 0.001). The values of enhancing and nonenhancing lesions were not different, whereas enhancing lesions had lower FA (p < 0.001). T1-hypointense lesions had higher and lower FA than T1-isointense lesions (p < 0.001). NAWM of patients had higher and lower FA than white matter of controls (p = 0.01). Significant correlations were found between T1 and T2 lesion volume and and FA of lesions and NAWM. In the overall patient sample, a moderate correlation was also found between lesion and the Expanded Disability Status Scale score (r = 0.28, p = 0.01). However, the r value of this correlation was 0.48 in patients with secondary progressive MS, whose disability was also correlated with average lesion FA (r = −0.50). Conclusions The results of this study show that DTI is able to identify MS lesions with severe tissue damage and to detect changes in the NAWM. They also indicate that DTI-derived measures are correlated with clinical disability, especially in patients with secondary progressive MS, thus suggesting a role for DTI in monitoring advanced phases of the disease.

White matter damage in Alzheimer's disease assessed in vivo using diffusion tensor magnetic resonance imaging

Objective: To investigate the extent and the nature of white matter tissue damage of patients with Alzheimers disease using diffusion tensor magnetic resonance imaging (DT-MRI). Background: Although Alzheimers disease pathology mainly affects cortical grey matter, previous pathological and MRI studies showed that also the brain white matter of patients is damaged. However, the nature of Alzheimers disease associated white matter damage is still unclear. Methods: Conventional and DT-MRI scans were obtained from16 patients with Alzheimers disease and 10 sex and age matched healthy volunteers. The mean diffusivity (D̅), fractional anisotropy (FA), and inter-voxel coherence (C) of several white matter regions were measured. Results: D̅ was higher and FA lower in the corpus callosum, as well as in the white matter of the frontal, temporal, and parietal lobes from patients with Alzheimers disease than in the corresponding regions from healthy controls. D̅ and FA of the white matter of the occipital lobe and internal capsule were not different between patients and controls. C values were also not different between patients and controls for any of the regions studied. Strong correlations were found between the mini mental state examination score and the average overall white matter D̅ (r=0.92, p<0.001) and FA (r=0.78; p<0.001). Conclusions: White matter changes in patients with Alzheimers disease are likely to be secondary to wallerian degeneration of fibre tracts due to neuronal loss in cortical associative areas.

Magnetisation transfer ratio and mean diffusivity of normal appearing white and grey matter from patients with multiple sclerosis

OBJECTIVE To assess the feasibility of a new technique based on diffusion anisotropy to segment white and grey matter of the brain. To use this technique to measure the mean diffusivity (D̄) and magnetisation transfer ratio (MTR) of normal appearing white matter (NAWM) and grey matter (NAGM) from patients with multiple sclerosis. METHODS Dual echo turbo spin echo, MT, and diffusion weighted scans of the brain were obtained from 30 patients with multiple sclerosis and 18 sex and age matched healthy controls. After image coregistration and removal of T2 visible lesions, white and grey matter were segmented from 10 supratentorial slices using diffusion anisotropy thresholds. Histograms of the average MTR and D̄ were created for normal white and grey matter of controls and NAWM and NAGM of patients with multiple sclerosis. RESULTS All the MTR histogram derived metrics of the NAWM from patients with multiple sclerosis were significantly lower than those of white matter from controls. The peak height of the D̄histogram of NAWM from patients with multiple sclerosis was also significantly different from that of normal white matter. The average MTR, the peak location of the MTR histogram, and peak height of theD̄ histogram of the NAGM of patients with multiple sclerosis were significantly lower than the corresponding quantities of grey matter from controls. CONCLUSIONS A technique was developed for segmenting white and grey matter with the potential for improving the understanding of the pathophysiology of many neurological conditions. Its application to the study of multiple sclerosis confirms the presence of a diffuse tissue damage in the NAWM of these patients and suggests that subtle changes also occur in the NAGM.

Pathologic damage in MS assessed by diffusion-weighted and magnetization transfer MRI

Objective: To compare diffusion characteristics of MS lesions, normal-appearing white matter (NAWM) from patients, and normal white matter from control subjects, and to investigate the correlations between the magnetization transfer ratio (MTR) and a directionally averaged tissue water diffusion coefficient (D¯) in patients. Background: MS and other pathologic processes that modify tissue integrity can result in abnormal diffusion of water molecules detectable by diffusion-weighted imaging (DWI). Methods: Conventional dual-echo and DWI scans were obtained from 35 patients with relapsing-remitting MS and 24 healthy control subjects. MT scans were also obtained from the patients. After coregistration of all scans, MTR and D¯ values from MS lesions and NAWM in different regions were marked using the dual-echo scans as a reference. D¯ values from the same brain regions in control subjects were acquired. Histograms of MTR and D¯ were also produced. Results: Patients with MS had significantly higher D¯ values in all the areas studied. Moreover, histogram metrics (peak height, peak site, and average D¯) from patients were substantially different from those of control subjects. In patients, average lesion D¯ and MTR were markedly different from those in the NAWM. There was an inverse correlation between average lesion MTR and D¯ inside lesions, whereas no correlation was found for average MTR and D¯ taken from the histograms. Conclusions: DWI detects severe tissue disruption inside lesions and subtle widespread abnormalities in NAWM in patients with relapsing-remitting MS. MT and DWI may provide information about different aspects of brain pathology in MS.

Quantification of tissue damage in AD using diffusion tensor and magnetization transfer MRI

The authors measured mean diffusivity (D̄) and magnetization transfer ratio (MTR) of the brain from 18 patients with AD and 16 healthy control subjects. The peak heights of cortical gray matter (cGM) D̄ (p < 0.001) and MTR (p < 0.001) histograms were lower and average cGM D̄ (p < 0.01) higher in patients with AD than in control subjects. A composite MR score based on brain volume and cGM MTR peak height was correlated with patient cognitive impairment (r = 0.65, p = 0.003). This preliminary study presents a novel approach to quantify AD-related tissue damage in-vivo.

The contribution of voxel-based morphometry in staging patients with mild cognitive impairment

Objective: To assess whether different patterns of regional gray matter loss in patients with mild cognitive impairment (MCI) are associated with different risks of conversion to Alzheimer disease (AD), using MRI and voxel-based morphometry (VBM). Methods: The authors recruited 22 patients with MCI, 22 patients with probable AD, and 20 healthy subjects (HS). T1 volumes from each subject were postprocessed according to an optimized VBM protocol. All patients were clinically followed up (mean [SD] time = 28.7 [5.7] months), and patients with MCI were reclassified into two groups (converters and nonconverters to AD). Results: When comparing patients with AD to HS, widespread areas of reduced gray matter density were found predominantly in temporal, frontal, and parietal lobes and in the insula. Comparing MCI converters and nonconverters with HS, the converters showed more widespread areas of reduced gray matter density than nonconverters, with a pattern of abnormalities similar to that seen in patients with AD. Conversely, when comparing the same groups with patients with AD, MCI nonconverters showed a pattern of gray matter density similar to that of HS. Areas of decreased gray matter density were also found in MCI converters compared with nonconverters. Conclusions: Different patterns of gray matter density distribution in patients with mild cognitive impairment may be associated to different rates of conversion to Alzheimer disease.

Weekly diffusion-weighted imaging of normal-appearing white matter in MS.

Article abstract To elucidate the dynamics and the nature of normal-appearing white matter (NAWM) changes preceding new lesion formation in MS, the authors obtained weekly diffusion-weighted images for 12 weeks from 6 patients. NAWM areas subsequently involved by enhancement had a significant increase in mean diffusivity values starting 6 weeks before the appearance of enhancement (p values ranging between < 0.0001 and 0.04). This suggests that focal edema and demyelination play a part in the NAWM changes preceding new lesion formation in MS.

The physical basis of diffusion-weighted MRI

Diffusion-weighted (DW) magnetic resonance imaging (MRI) is the only technique that permits a non-invasive in vivo assessment of water molecular diffusion, which reflects tissue configuration at a microscopic level. Therefore, this technique appears to be particularly useful in monitoring brain abnormalities. However, the quantitative measurement of diffusion is not without problems, which may limit the widespread use of diffusion-weighted MRI. In this report, the phenomenon of diffusion is described, together with its effect on the nuclear magnetic resonance signal. The concepts of diffusion anisotropy and diffusion tensor are also introduced, and the technical and hardware requirements are discussed.

Long-term clinical outcome of primary progressive MS: Predictive value of clinical and MRI data

The authors sought to identify clinical and MRI predictors of outcome in primary progressive multiple sclerosis (PPMS). Clinical and MRI assessments were performed at baseline and 2 and 5 years (clinical only). At baseline, disease duration, expanded disability status scale (EDSS) and brain volume predicted outcome. Adding short-term change variables, baseline EDSS, changes in T2* lesion load and cord area, and number of new lesions were predictive. Clinical and MRI variables predict long-term outcome in PPMS.

Intra-voxel and inter-voxel coherence in patients with multiple sclerosis assessed using diffusion tensor MRI

Abstract. Previous diffusion tensor magnetic resonance imaging (DT-MRI) studies reported mean diffusivity (n