Clinicopathological correlations for black holes: an MRI marker for axonal loss?
Magnetic resonance imaging (MRI) has proved to be a very sensitive method for detecting multiple sclerosis (MS) lesions in the brain.1 Hyperintense lesions on T2weighted images correspond histopathologically to MS lesions.2 T2-weighted hyperintense lesion load measurement is well established as a surrogate outcome measure in clinical trials of MS, even when its correlation with disability is low.3,4 The low (but statistically significant) correlation of T2-weighted lesion load with the clinical disability of MS patients reflects (beside problems with clinical localization and scoring) the low histopathological substrate of T2-weighted hyperintense lesions; any alteration in brain tissue composition can increase signal, including processes such as inflammation, oedema, mild to severe demyelination, axonal loss and remyelination. To improve the correlation between MRI and clinical disability, other magnetic resonance markers are needed. As axonal loss is the most likely correlate of increased disability, markers for this are especially needed. One available technique is magnetic resonance spectroscopy (MRS), where the concentration of N-acetylaspartate (NAA) can be used as a marker of functioning axons. While the use of MRS has yielded important insights (e.g. into the role of the normal-appearing white matter (NAWM)), the technique is technically demanding and has poor spatial resolution.