Brain metabolite profiles of T1-hypointense lesions in relapsing-remitting multiple sclerosis

Abstract

Background and purpose: Persistent T1-hypointense lesions ("black holes") are thought to represent permanent damage of brain parenchyma. We attempted to ascertain whether the metabolic profiles of these hypointense areas support this hypothesis and whether these profiles correlate with these hypointense findings.

Methods: Four patients with relapsing-remitting multiple sclerosis and four matched control volunteers underwent MR imaging and 3D proton MR spectroscopy. Absolute levels of N-acetylaspartate (NAA), creatine, and choline (Cho) were obtained in 0.19 cm(3) voxels containing 14 T1-hypointense lesions (average volume, 0.4 cm(3); range, 0.2-1.0 cm(3)) in patients. Metabolite levels were analyzed, by using Pearson correlation, against their respective lesions' hypointensity relative to the surrounding normal-appearing white matter.

Results: Moderate correlation, r = 0.56, was found between the NAA level and MR imaging hypointensity. Of the 14 lesions studied, 12 were deficient in NAA and 11 had excess Cho compared with corresponding brain regions in control volunteers. Only one lesion was significantly deficient in all three metabolites, indicative of total damage or matrix loss.

Conclusion: No relationship was found between the hypointensity of the lesions and their metabolic profile. Specifically, lesions with the same hypointensity on T1-weighted MR images were metabolically variable (ie, displayed disparate metabolite levels and behavior). Also, although 86% of the lesions exhibited abnormally low NAA, 71% also had increased Cho. This indicates that although neuronal damage had already occurred (lower NAA), these lesions were still "smoldering" with active membrane turnover (high Cho), most likely because of de- and remyelination, indicative of shadow plaques (remyelinated lesions). Consequently, relapsing-remitting hypointense lesions represent neither final-stage nor static pathologic abnormality.

Fig 1.

T1-weighted MR images of a 43-year-old female patient with multiple sclerosis, superimposed with the size and location of the 8_LR ×10_AP cm² MR spectroscopy volumes of interest. The volumes of interest contained an approximately 1-cm diameter T1-hypointense lesion (arrow); the metabolite concentration ratios were NAA = 0.18, Cr = 0.21, and Cho = 0.25. The image contrast ratio was 0.76. A, Sagittal view. B, Axial view. C, Real part (1.7–3.7 ppm range) of a 6 × 6 proton spectra matrix (0.2 cm³ voxels) from the 3 × 3 cm² dashed box shown in B, containing the lesion (circle).

Fig 2.

Corresponding T1-weighted MR images of a matched control participant, superimposed with the outline of the 8_LR ×10_AP cm² proton MR spectroscopy volumes of interest. A, Sagittal view. B, Axial view. C, Real part of a 6 × 6 proton spectra matrix (0.2 cm³ voxels) from the 3 × 3 cm² dashed box shown in B. Circle indicates the region corresponding to the lesion shown in Figure 1C. The spectra span the same chemical shift (1.7–3.7 ppm) and intensity range as those in Figure 1C.

Fig 3.

Contrast ratio (CR) of the lesions’ signal intensity versus metabolite concentration ratios (MCR) of NAA, Cr, and Cho for A, the 14 persistent T1-hypointense lesions in all patients, and B, six persistent T1-hypointense in the same 41-year-old male patient in whom images and spectra were obtained during the MR imaging–MR spectroscopy session. In both figures, hypointensity was characterized as severe if it was darker than the contrast ratio of normal-appearing gray matter (< 0.83), in accordance with van Walderveen et al (15).

Fig 4.

Cho versus NAA metabolite concentration ratios (MCR) for the 14 T1-hypointense lesions from all patients. Shaded oval highlights a region with a narrow 50% range (1.0–1.5) of elevated Cho levels, corresponding to a broad ±450% range (0.2–0.9) of low NAA levels.