Neuronal damage in T1-hypointense multiple sclerosis lesions demonstrated in vivo using proton magnetic resonance spectroscopy

Hypointense T1 lesions in multiple sclerosis patients correlate with axonal loss at autopsy and biopsy. We evaluated the chemical substrate of hypoint ense T1 lesions by using in vivo proton magnetic resonance spectroscopy, an d analyzed the spectroscopic correlate of increased T1-relaxation time meas urements. Localized proton magnetic resonance spectroscopy and T1-relaxatio n time measurements were performed in lesions, selected on TI-weighted spin -echo magnetic resonance images according to degree of hypointensity, in no rmal appearing white matter (NAWM) and in normal white matter of controls. In NAWM, prolongation of T1-relaxation time and a decrease in N-acetylaspar tate (NAA) were present, compared with normal white matter. Severely hypoin tense lesions showed a lower concentration of NAA and creatine compared wit h NAWM and a lower concentration of NAA compared with isointense to mildly hypointense lesions. NAA concentration correlated with degree of hypointens ity of lesions and with TI-relaxation time within the spectroscopic voxel. Our results provide the first in vivo evidence of axonal damage in severely hypointense T1 lesions in multiple sclerosis patients. T1-relaxation time correlates with the concentration of NAA in both multiple sclerosis lesions and NAWM, indicating that this parameter deserves further evaluation to mo nitor disease progression.