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Abstract
Non-invasive molecular imaging techniques can enhance diagnosis to achieve successful treatment, as well as reveal underlying pathogenic mechanisms in disorders such as multiple sclerosis (MS). The cooperation of advanced multimodal imaging techniques and increased knowledge of the MS disease mechanism allows both monitoring of neuronal network and therapeutic outcome as well as the tools to discover novel therapeutic targets. Diverse imaging modalities provide reliable diagnostic and prognostic platforms to better achieve precision medicine. Traditionally, magnetic resonance imaging (MRI) has been considered the golden standard in MS research and diagnosis. However, positron emission tomography (PET) imaging can provide functional information of molecular biology in detail even prior to anatomic changes, allowing close follow up of disease progression and treatment response. The recent findings support three major neuroinflammation components in MS: astrogliosis, cytokine elevation, and significant changes in specific proteins, which offer a great variety of specific targets for imaging purposes. Regardless of the fact that imaging of astrocyte function is still a young field and in need for development of suitable imaging ligands, recent studies have shown that inflammation and astrocyte activation are related to progression of MS. MS is a complex disease, which requires understanding of disease mechanisms for successful treatment. PET is a precise non-invasive imaging method for biochemical functions and has potential to enhance early and accurate diagnosis for precision therapy of MS. In this review we focus on modulation of different receptor systems and inflammatory aspect of MS, especially on activation of glial cells, and summarize the recent findings of PET imaging in MS and present the most potent targets for new biomarkers with the main focus on experimental MS research.
Highlights
Multiple sclerosis (MS) is the most common disabling neurologic disease of young people, afflicting approximately a quarter of million Americans (Anderson et al, 1992; Islam et al, 2006; Brody, 2012; Ransohoff et al, 2015)
Factors inducing inflammation vary between central nervous system (CNS) related diseases, there is evidence that convergence mechanisms are accountable for the sensing, transduction, and amplification of inflammatory processes that eventually lead to the production of neurotoxic mediators (Glass et al, 2010)
Inflammation and glial activation play an important role in numerous neurodegenerative diseases, such as Alzheimer’s disease, Parkinson disease, amyotrophic lateral sclerosis and MS
Summary
Multiple sclerosis (MS) is the most common disabling neurologic disease of young people, afflicting approximately a quarter of million Americans (Anderson et al, 1992; Islam et al, 2006; Brody, 2012; Ransohoff et al, 2015). Combined PET/MRI imaging with high specificity to MS lesions, would have a potential to become a practical tool in clinics to follow up the treatment of MS patients and increase cost-effectiveness. There is growing amount of evidence from both MRI and histological studies proposing that the axonal degeneration contributes to the development of clinical disability (Edgar and Nave, 2009; Nave, 2010) These interesting facts further highlight the need of specific markers for imaging of disease stage. The current literature suggest that [11C]MeDAS is the most preferred PET agent so far to highlight the lesions as well as the myelin content in the spinal cord in motor disability related MS (de Paula Faria et al, 2014a) To this point the only PET tracer used to image myelin in MS patients is [11C]PIB, a tracer widely utilized to visualize β-amyloid plaques in Alzheimer’s disease (Stankoff et al, 2011; Zhang et al, 2014). Achieving precision medicine in MS requires high quality data, large samples, and consistent interdisciplinary approach
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