Serial proton magnetic resonance spectroscopic imaging, contrast‐enhanced magnetic resonance imaging, and quantitative lesion volumetry in multiple sclerosis

Abstract

Serial magnetic resonance (MR) studies that included proton MR spectroscopic imaging (MRSI), contrast-enhanced MR imaging (MRI), and lesion volumetric studies were performed on 25 multiple sclerosis (MS) patients with mild to modest clinical deficits. Each patient was scanned at varying intervals for up to 2 years, resulting in a total of 124 usable MR sessions. In these longitudinal studies, metabolic changes were observed on MRSI for some subjects before the appearance of lesions on MRI scanning. Regional changes in metabolite levels were observed to be dynamic and reversible in some patients. Transient changes in N-acetylaspartate (NAA) levels were sometimes found in acute plaques and indicate that a reduced NAA level does not necessarily imply axonal loss. An inverse correlation between the average NAA within the spectroscopic volume and the total lesion volume in the whole brain was observed. This negative correlation implies that NAA can serve as an objective marker of the disease burden. Strong lipid peaks in the absence of gadolinium enhancement and MRI-defined lesions were observed in 4 patients. This observation suggests that demyelination can occur independent of perivenous inflammatory changes and supports the presence of more than one pathophysiological process leading to demyelination in MS.

Recent Advances in Magnetic Resonance Neurospectroscopy

“…127,[153][154][155][156][157][158][159][160][161][162][163][164] In general, the CVs of the metabolites were higher in the CSI studies than the single-voxel acquisitions. For example, Marshall et al 155 reported CVs for NAA of ϳ20% at a TE of 25 ms at 1.5 T and ϳ12% for a TE of 145 ms.…”

Proton MR Spectroscopy in Brain Metabolic Disorders

“…In acute demyelination, decreases in Cr can also be seen [6]. Short echo time spectra give evidence for transient increases in mI [49] and lipids [50], also released during myelin breakdown. After the acute phase, metabolic modifications in the demyelinating lesion show a variable time course [6].…”

Imaging of multiple sclerosis: Role in neurotherapeutics

“…13,14 Unfortunately, these changes have not been robust enough to use prospectively. Focal increases in choline and the appearance of signals on MR spectroscopic imaging (MRSI) consistent with alterations in lipids or other myelin associated macromolecules also precede lesion formation by several months, 15,16 to suggest that focal disruptions of tissue integrity anticipate enhancements. It remains unclear whether these changes reflect some primary intrinsic tissue process that eventually signals a secondary influx of inflammatory cells, or whether they reflect microscopic inflammatory change beyond the resolution of conventional imaging that must first build before a cascading inflammatory response is evident.…”

“…8 However, a significant proportion of the larger lesions that disappear or decrease in size later than 6 months may do so at the expense of gliosis and atrophy. [77][78][79][80] The potential reversible nature of the pathologic process associated with T1-hypointense lesions is supported by correlation with serial spectroscopic assessments in which recovery of axonal integrity [N-acetyl aspartate (NAA)] suggests transient dilutional effects of edema and metabolic dysfunction of axons in recovering black holes 15 or permanent reduction in NAA correlated with sustained black holes and accumulating clinical disability. 81,82 Certainly, those lesions that show the most profound hypointensity on T1-weighted post mortem images correlate pathologically with the most profound demyelination and axonal loss.…”

“…Regional increases in Cho and mobile lipids may precede conventional T2-weighted MRI-based lesion detection by several months. 15,16 This suggests that MRS may be more sensitive than MRI in defining microscopic regions of perivenular inflammatory demyelination, or that locally abnormal cellular metabolism or tissue integrity mark regions for a secondary inflammatory insult. Recently formed enhancing lesions in previously MRI NAWM usually show highly dynamic metabolite changes that include increased Cho and myelin breakdown products, 96,97 increased myo-inositol and glutamate plus glutamine in larger ring-enhanced lesions, 98 lactate and diminished NAA.…”