Quantification of Intrinsic Lesion Damage

In chronic T2-hyperintense lesions, MT MRI and DW MRI studies have shown variable degrees of MTR, FA and NAA reduction and MD increase (4,120,121). All these values vary dramatically across individual lesions. These abnormalities are more pronounced in lesions that are hypointense on Tl-weighted images and in patients with the most disabling courses of the disease (4,120,122,123). The variability of MTR, MD, and FA values seen in MS lesions suggests that different proportions of lesions, with different degrees of structural damage might contribute to the evolution of the disease. This concept is supported by a three-year follow-up study (124) showing that newly formed lesions from SPMS patients have more severe MTR deterioration than those from mildly disabling RRMS patients.

New enhancing lesions have different range of MTR values, according to their size, modality, and duration of enhancement. In particular, MTR is higher in homogeneously enhancing lesions than in ring-enhancing lesions (125); in lesions enhancing on a single scan than in those enhancing on two or more serial scans (108) and in lesions enhancing after the injection of a TD of Gd than in those enhancing after the injection of a standard dose (109). DW MRI characteristics of enhancing lesions are less well defined. While FA values are consistently lower in enhancing than in nonenhancing lesions (126,127), conflicting results have been achieved when comparing ADC or MD between these two lesion populations. While some studies reported higher ADC or MD values in nonenhancing than in enhancing lesions (126,128), others, based on larger samples of patients and lesions, did not report any significant difference between the two lesion populations (127,129). The heterogeneity of enhancing lesions has been also underlined by the demonstration that water diffusivity is markedly increased in ring-enhancing lesions when compared with homogeneously enhancing lesions (130), or in the nonenhancing portions of enhancing lesions when compared with the enhancing portions (130).

1H-MRS of acute MS lesions at both short and long echo times reveals increases in Cho and Lac resonance intensities (121,131), which reflect the releasing of membrane phospholipids and the metabolism of inflammatory cells, respectively. In large acute demyelinating lesion decreases of Cr can also be seen (121). Short echo time spectra can detect transient increases in visible lipids released during myelin breakdown and mI (132). All these changes are usually associated with a decrease in NAA. After the acute phase and over a period of days to weeks there is a progressive reduction of raised Lac resonance intensities to normal levels. Resonance intensities of Cr also return to normal within a few days. Cho, lipid, and mI resonance intensities return to normal over months. The signal intensity of NAA may remain decreased or show partial recovery, starting soon after the acute phase and lasting for several months (121,131,133).

A progressive decrease of MTR values and an increase of MD values can be detected in regions that will develop new lesions (134-139). Using 1H-MRS, Cho increase, probably reflecting an altered myelin chemistry or the presence of inflammation, and a decrease in NAA have been also shown in prelesional NAWM (132,140,141).

Average lesion MTR has been found to be lower in patients with RRMS than in those with CIS suggestive of MS (93,142), whereas no differences have been found in cross-sectional studies between patients with RRMS and those with SPMS (142) or between patients with SPMS and those with PPMS (110).

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