Multiple Sclerosis diagnosis and prognosis. Brain MRI and PET CT. Part 1 of 2. 11

Multiple Sclerosis diagnosis and prognosis. Brain MRI and PET CT. Part 1 of 2. 11

Multiple Sclerosis diagnosis and prognosis. Brain MRI and PET CT. Part 1 of 2. 11

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You are a leader in brain imaging technologies.You founded the world-leading Center for Functional MRI of the Brain at Oxford University. Dr. Anton Titov, MD. You built a GlaxoSmithKline's internal clinical imaging program at the Hammersmith Hospital campus of Imperial College London. Dr. Paul M. Matthews, MD. Then you led GSK's clinical development program in multiple sclerosis. Dr. Anton Titov, MD. Now you have come back to academic research. You lead the Division of Brain Sciences at Imperial College London. Dr. Anton Titov, MD. Where do you see MRI brain imaging technology progressing in the next 5 to 10 years? Well, you've been very generous in your introduction, Anton. Dr. Paul M. Matthews, MD. Just for the record, I led a multiple sclerosis imaging program within GSK, but not all of multiple sclerosis. That program at the time was much broader. The question of where MRI brain imaging is going is an interesting question. Dr. Paul M. Matthews, MD. Because I think we are in a very exciting time. First, the range of modalities that we can use to explore multiple sclerosis and its consequences continues to expand. Over the last decade we have seen the advent of optical coherence tomography [OCT]. OCT is an increasingly important tool in the evaluation of progression in patients with multiple sclerosis. Optical coherence tomography has ability to visualize and accurately quantify the nerve fiber layer in the retina and the ganglion cell layer. Both these retinal layers show changes with progression of multiple sclerosis. A second area of progress in brain imagine of multiple sclerosis also exists. Dr. Paul M. Matthews, MD. We have seen an expansion of the range of diagnostic modalities. They are beginning to be used more commonly in the clinical trials of multiple sclerosis. This is a Positron Emission Tomography, or PET, methods. A decade ago, there were early demonstrations of possible utility of fluorodeoxyglucose PET. This is a classic glucose scan. PET CT provides some measure of the density and function of synapses of brain cells. More recently, work has extended out in a number of groups. Dr. Paul M. Matthews, MD. We apply a range of special molecular tracers that are sensitive to aspects of microglial and astrocyte activation in the brain. We look at expression of a molecule known as the 18 kDa mitochondrial translocator protein. This work already is providing important insight into the multiple sclerosis. Dr. Paul M. Matthews, MD. Our work highlights the heterogeneity of chronic lesions in multiple sclerosis. We showed that some multiple sclerosis lesions are associated with pronounced microglial activation. Other lesions are not. This shows the degree to which microglia in the the brain cortex can be activated. We are beginning to define the cortical lesions. Dr. Anton Titov, MD. Multiple sclerosis lesions are defined by microglial activation. Other lesions are defined on the basis of MRI. Both methods of diagnosis are maybe related. MRI and PET possibly provide additional diagnostic measures. PET and MRI help to understand the prognosis of patients with progressive multiple sclerosis. But we need to do more research, because this data is early. More recent PET imaging results suggest an important multiple sclerosis treatment assessment. There may be practical ways of providing an additional index of myelin integrity in the brain. There are classic amyloid markers that are now used for diagnostic stratification of patients with memory complaints. Dr. Paul M. Matthews, MD. We may be able to repurpose amyloid markers as at least qualitative indices of myelin density. This diagnostic methods can supplement measures from MRI techniques, such as magnetization transfer. Dr. Anton Titov, MD. There is also a rich future for applying other PET radio-ligands. Some PET ligands are sensitive, for example, to the presence of inhibitory synapses in the brain. Dr. Paul M. Matthews, MD. There are also more options to improve diagnostic and treatment precision in patients with multiples sclerosis.

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