Lesion heterogeneity in multiple sclerosis: a study of the relations between appearances on T1 weighted images, T1 relaxation times, and metabolite concentrations

Abstract

Objectives-Multiple sclerosis lesions appear as areas of high signal on T2 weighted MRI. A proportion of these lesions, when viewed on T1 weighted MRI, appear hypointense compared with surrounding white matter. These hypointense T1 lesions are thought to represent areas of greater tissue damage compared with the more non-specific, total T2 lesion load. This study aimed to better characterise the properties of high signal T2 lesions with diVering appearances on T1 weighted MRI using quantitative MR techniques. Methods-Eleven patients with secondary progressive multiple sclerosis were studied. Two high signal T2 lesions were selected from each patient-one of which appeared hypointense and one isointense on a T1 weighted image. A voxel was positioned around each lesion and for this volume of brain the metabolite concentrations were estimated using proton MR spectroscopy ( 1 H-MRS) and the T1 relaxation time within each voxel calculated from a T1 map generated using a multislice technique. Results-Compared with isointense T1 lesions, hypointense T1 lesions exhibited a significantly lower absolute concentration of N-acetyl derived metabolites (tNAA) and a significantly higher absolute concentration of myo-inositol (Ins). T1 relaxation time correlated significantly with both tNAA (r=−0.8, p < 0.001) and Ins (r=0.5, p=0.012). There was no correlation between T1 relaxation times and creatine/ phosphocreatine or choline containing compounds. Conclusions-Prolonged T1 relaxation times seem to reflect the severity of axonal damage or dysfunction (inferred by a low tNAA) and possibly also gliosis (inferred by a high Ins) in chronic multiple sclerosis lesions. (J Neurol Neurosurg Psychiatry 2000;68:627-632)

Biomarkers and surrogate outcomes in neurodegenerative disease: Lessons from multiple sclerosis

“…Peaks at 0.9 and 1.3 ppm are also seen in acute lesions and resolve over several months 36 ; these are attributed to lipid breakdown products in association with demyelination An increase in myoinositol (Ins) is seen in MS lesions and is more marked in T1 hypointense lesions. 37 It is also observed in NAWM, in which the elevation has been correlated with disability in MS patients with both short and long disease durations. 38,39 Ins is produced by glial cells and is a potential marker of astrocytosis, gliosis, or possibly microglial activation.…”

Diffusely Abnormal White Matter in Progressive Multiple Sclerosis: In Vivo Quantitative MR Imaging Characterization and Comparison between Disease Types

“…In MS, T1 has been shown to be increased in different pathologic processes, most prominently axonal damage but also edema, demyelination, and gliosis. 4,[11][12][13][14][15][16] MTR mapping produces voxelwise maps of the relative amount of signal-intensity decrease that results from adding a magnetization-preparation prepulse to a pulse sequence. The MTR is a semiquantitative measure that is ultimately determined by more fundamental parameters such as the fraction of bound pool protons, the magnetization exchange rate between bound and free protons, and the relaxation rates.…”

Imaging of multiple sclerosis: Role in neurotherapeutics

“…101 These permanent T1-hypointense lesions may have increased concentrations of myo-inositol, possibly as an indication of gliosis. 100,102 More global reductions of NAA occur in MRI-defined NAWM adjacent to visible plaques, 103,104 in larger white matter expanses with limited MRI-visible lesions, 15,105 and in whole MS brain. 106 These changes in NAWM are not as profound early in the disease 107 as they are late in progressive cases.…”

“…Diminished NAA levels are particularly common in lesions with significant T1 hypointensiy. 81,100 In persistently T1-hypointense lesions, reduced NAA indicates irreversible axonal loss. 101 These permanent T1-hypointense lesions may have increased concentrations of myo-inositol, possibly as an indication of gliosis.…”