Magnetic resonance (MR) imaging is often used to characterize and quantify multiple sclerosis (MS) lesions in the brain and spinal cord. The number and volume of lesions have been used to evaluate MS disease burden, to track the progression of the disease and to evaluate the effect of new pharmaceuticals in clinical trials. Accurate identification of MS lesions in MR images is extremely difficult due to variability in lesion location, size and shape in addition to anatomical variability between subjects. Since manual segmentation requires expert knowledge, is time consuming and is subject to intra- and inter-expert variability, many methods have been proposed to automatically segment lesions. The objective of this study was to carry out a systematic review of the literature to evaluate the state of the art in automated multiple sclerosis lesion segmentation. From 1240 hits found initially with PubMed and Google scholar, our selection criteria identified 80 papers that described an automatic lesion segmentation procedure applied to MS. Only 47 of these included quantitative validation with at least one realistic image. In this paper, we describe the complexity of lesion segmentation, classify the automatic MS lesion segmentation methods found, and review the validation methods applied in each of the papers reviewed. Although many segmentation solutions have been proposed, including some with promising results using MRI data obtained on small groups of patients, no single method is widely employed due to performance issues related to the high variability of MS lesion appearance and differences in image acquisition. The challenge remains to provide segmentation techniques that work in all cases regardless of the type of MS, duration of the disease, or MRI protocol, and this within a comprehensive, standardized validation framework. MS lesion segmentation remains an open problem.
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