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Summary: We report a semiautomated postprocessing method based on magnetization transfer MR imaging that can quantify the extent of global disease in patients with multiple sclerosis. The technique combines segmentation and quantitative analysis of imaging data reflecting the structural integrity of white matter. Applications of this technique may include assessment of dis- ease progress and of the efficacy of experimental therapeutic intervention. The height of the histogram peak corresponding to white matter was found to be lowered in patients with multiple sclerosis and the overall distribution of magnetization transfer ratios was shifted to lower values. The recently introduced technique known as magnetization transfer (MT) imaging may be more sensitive to the presence of multiple scle- rosis (MS) than are conventional magnetic res- onance (MR) imaging techniques. Animal ex- periments in a model of wallerian degeneration with histopathologic confirmation have sug- gested that MT imaging is sensitive to structural changes in white matter that are not apparent by conventional imaging (1). In MS, abnormal- ities have been detected not only in plaques but also in areas of white matter that appeared nor- mal on conventional MR images (2-4). These abnormalities in normal-appearing white matter have been attributed to the microscopic paren- chymal disease that has been found in histo- logic studies. Estimation of the extent (or burden, as as- sessed radiologically) of disease in MS is desir- able in order to study the natural course of the disease and to evaluate the effects of treatment. Little correspondence has been established be- tween clinical gradations of the disease and ex- tent of disease apparent at MR imaging: some patients with markedly abnormal MR studies are clinically asymptomatic while others with only minimal disease apparent on MR images are profoundly impacted by the disease. These dis- crepant findings may be explained by the ob- servation that clinical assessment of disease ex- tent is heavily weighted toward spinal cord and motor tract involvement. It is clear that disease burden in a clinical sense may be quite different from, and not associated with, disease extent as seen on MR images. In the case of MS, the lack of clinical symptoms may actually mask the progress of disease. Recently, we showed that analysis of three- dimensional MT data from a slab of unseg- mented cranial tissue by means of MT ratio histograms could be used to estimate the total extent of MS in that slab (5). The present work combines segmentation of total brain paren- chyma with generation of an MT ratio histo- gram, resulting in a more comprehensive as- sessment of disease burden.

Global Volumetric Estimation of Disease Burden in Multiple Sclerosis Based on Magnetization Transfer Imaging