Leading expert in multiple sclerosis and brain imaging, Dr. Paul Matthews, MD, explains how advanced MRI and PET CT technologies are revolutionizing diagnosis and prognosis. He details the use of optical coherence tomography to track retinal nerve fiber changes. Dr. Paul Matthews, MD, highlights novel PET tracers that detect microglial activation and myelin integrity. These imaging modalities provide critical insights into disease heterogeneity and progression. This research is paving the way for more precise and personalized treatment strategies for patients.
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Advanced Brain Imaging in Multiple Sclerosis: MRI, PET CT, and OCT
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- Key Imaging Modalities for MS
- Role of Optical Coherence Tomography
- PET CT Advancements and Tracers
- Microglial Activation and Lesion Heterogeneity
- Future Diagnostic and Prognostic Tools
- Full Transcript
Key Imaging Modalities for MS
Multiple sclerosis diagnosis and monitoring rely heavily on advanced brain imaging technologies. Dr. Paul Matthews, MD, a leader in the field, discusses the expanding range of modalities. Magnetic resonance imaging (MRI) remains a cornerstone for visualizing lesions and disease activity. However, newer techniques like Positron Emission Tomography (PET) and optical coherence tomography (OCT) are providing complementary data. These tools offer a more complete picture of the disease's impact on the brain and nervous system.
Role of Optical Coherence Tomography
Optical coherence tomography is an increasingly vital tool for evaluating multiple sclerosis progression. As Dr. Paul Matthews, MD, explains, OCT visualizes and quantifies specific layers of the retina. It accurately measures the nerve fiber layer and the ganglion cell layer. Both of these retinal structures show measurable changes as multiple sclerosis advances. This provides clinicians with a non-invasive window into neurodegeneration, offering a valuable prognostic indicator.
PET CT Advancements and Tracers
Positron Emission Tomography combined with CT (PET CT) is emerging as a powerful diagnostic tool. Dr. Paul Matthews, MD, notes its growing use in clinical trials for multiple sclerosis. While fluorodeoxyglucose (FDG) PET scans measure synaptic activity and brain cell function, newer tracers are more specific. Special molecular tracers are now sensitive to microglial and astrocyte activation. These tracers target molecules like the 18 kDa mitochondrial translocator protein, providing deeper biological insights.
Microglial Activation and Lesion Heterogeneity
Research using novel PET tracers has revealed significant heterogeneity in multiple sclerosis lesions. Dr. Paul Matthews, MD, describes how this imaging shows pronounced microglial activation in some chronic lesions but not in others. This variation highlights the complex and variable nature of the neuroinflammatory process in MS. Defining cortical lesions by their microglial activity, in addition to standard MRI findings, offers a more nuanced understanding of disease pathology and its link to clinical progression.
Future Diagnostic and Prognostic Tools
The future of multiple sclerosis imaging involves repurposing existing tools and developing new ones. Dr. Paul Matthews, MD, suggests that classic amyloid PET markers could be used as qualitative indices of myelin density. This would supplement MRI techniques like magnetization transfer imaging. Furthermore, other PET radio-ligands sensitive to inhibitory synapses are on the horizon. According to Dr. Paul Matthews, MD, these advancements will significantly improve diagnostic precision and help tailor treatments more effectively for individual patients.
Full Transcript
Dr. Anton Titov, MD: You are a leader in brain imaging technologies. You founded the world-leading Center for Functional MRI of the Brain at Oxford University. You built GlaxoSmithKline's internal clinical imaging program at the Hammersmith Hospital campus of Imperial College London. Then you led GSK's clinical development program in multiple sclerosis. Now you have come back to academic research. You lead the Division of Brain Sciences at Imperial College London.
Where do you see MRI brain imaging technology progressing in the next 5 to 10 years?
Dr. Paul Matthews, MD: Well, you've been very generous in your introduction, Anton. 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. 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 the 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 imaging of multiple sclerosis also exists. 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 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. 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 multiple sclerosis. 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 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 Matthews, MD: We may be able to repurpose amyloid markers as at least qualitative indices of myelin density. This diagnostic method 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 Matthews, MD: There are also more options to improve diagnostic and treatment precision in patients with multiple sclerosis.