23 answers on predicting disease progression and MRI

Arman (centre) answering questions with support from Sophie and Luke at MSIF

Arman Eshaghi, a researcher from Iran, was awarded one of MSIF’s McDonald Fellowships in 2014. This award enables talented young MS researchers from emerging countries to work with leading researchers in MS.

Arman is currently based in UCL Institute of Neurology in London, working with Prof Olga Ciccarelli, Prof Alan Thompson, and Prof Daniel Alexander. He has answered questions on his area of expertise (Predicting disease progression using MRI and computer models) on MSIF’s Facebook account on Wednesday 16 December 2015.

We would like to say a huge thank you to Arman for his time and to everyone who sent us questions. We had more questions than it was possible to answer in one hour (we even overran by nearly 30 minutes!) so Arman has answered as many as he could.

Here is a write-up of the questions and answers, which we hope you will find useful. Please do consider making a donation using the link at the bottom of the page to support researchers like Arman.

Our first question comes via email, from Isabel in Portugal: What is MRI?

Magnetic Resonance Imaging or MRI is a non-invasive approach to acquire images from tissues inside the body. MRI is based on molecular properties of different tissues, and could show early changes in tissues that may not be evident by other medical imaging techniques (such as CT scan or X-rays).

Mehnaz asks on Facebook: How is an MRI scan interpreted? Do new relapses appear on the scan?

MRI scans are usually interpreted by a neuroradiologist who looks at the appearance of lesions in specific areas of the brain. Since MS lesions appear to have a specific distribution in different brain regions, and develop over time, MRI scans provide an important tool to monitor and play an important role in the diagnosis. New relapses may or may not appear on MRI, this is because MRIs can only pick up some changes happening in brain. With the development of more advanced technologies in MRI and perhaps other markers, this could change. Currently a relapse is defined by clinical changes, alone.

Tony, from the US asked: How long do you think it will be before the first really useful results of your research are known, and how accurately do you think you will be able to predict disease progression?

I will be working at the Institute of Neurology for the next three years at least. We hope to have first results ready in less than a year, although it may take a longer time for our results from our group and similar results from other groups to be translated into medical practice. MRI provides a more objective assessment of disease progression, as an example it can be used to monitor brain changes in drug trials. Therefore we hope to be able to use MRI to explain disease progression.

Lisa asks: How will the general public be able to access your research results?

I will let the MSIF team know when the results are published, and they will disseminate the information. If you are interested in hearing about the latest research in MS, you can sign up to the MS Research News newsletter.

One question that came up a lot over email was people telling us that even when the MRI shows no new lesions their symptoms are clearly getting worse. They would like to know why this happens.

There are different MRI techniques (which are called MRI sequences). Each of these show different aspects of the disease. However, there is always a part of the disease that is not accessible by MRI, such as inflammation in progressive MS, or subtle functional changes. Moreover lesions are shown using one MRI sequence in clinical practice, and more gradual tissue loss, such as loss of brain cells in grey matter may not be easily seen by clinical MRI. Therefore lesions could only be the tip of the iceberg of the ongoing disease activity.

Reginald says: Since starting on medication the relapse rate has pretty much come to a stop (says the MRI scan) but I feel like the disease is still progressing. Why is this?

Lesions tend to appear less during the progressive stage of MS. Usually at this phase, loss of brain cells (neurons) in addition to spinal cord cells play a more important role to determine disability. Therefore, lesions may not be associated with disability, at least during this stage.

Cathy, via Facebook: how trustworthy are MRIs on prediction of progression?

Currently the progression of MS is defined by changes in clinical symptoms and disability only (for example changes in the distance that you can walk without taking a break), we hope future research on more subtle changes in MRI can change this.

Daniel, also on Facebook: Why does the MRI matter, or should the focus be on ability/function? Is the location of a lesion an indicator of damage? Can you identify when a lesion causes a loss of function/ability? Are the effects of lesions cumulative? And how do you distinguish the effects of MS vs. aging?

You are right as not all symptoms that patients experience are related to MRI lesions. This is usually known as the paradox between clinical and radiological appearance of the disease. Lesions can only show an aspect of the disease. More subtle changes, such as the shrinkage in the brain, may not be easily picked up, at least with available MRI scanners in clinical centres. Moreover, human brain has a great potential to make up for damage, which makes it more complicated to draw a straight line between lesions and progression. To distinguish between aging and effect of MS in patients during research, we use healthy volunteers at the same age of patients.

Kris from Australia would like to know: Is MRI really effective in diagnosing MS?

MRI is the cornerstone of diagnosing MS, but for a small proportion of patients it doesn’t allow a straightforward diagnosis. These patients may be asked to have further follow up scans after a while to see if their results have changed.

Bergþóra asks: Is MRI suitable enough to determine whether a patient has relapsing-remitting MS or secondary progressive MS and therefore should receive a disease-modifying drug treatment or not?

To define the subtype of MS (RRMS or SPMS), neurologists usually look at the history of patients, and MRI does not play a primary role here. However, in my research we are trying to find the signature of these different subtypes which might help, in future, to explain each MS subtype in a more objective way.

Florence, from Canada is asking: How close are you in determining which individuals with MS are at a higher risk of developing early disability? How accurate do you expect these predictions to be?

Since there are multiple factors to determine the risk of disability, we do not expect to have a high accuracy in determining the risk of progression only relying on imaging. For example, we know that genetic factors, in addition to environmental factors (e.g., exposure to sunlight or some viruses) can play a role. We hope that in the future using a more holistic approach can provide risk of progression for each patient. Current classification of MS is based on clinical assessment and progression and is not based on MRI. MRI can be used to help in the diagnosis. My research could help to give MRI a higher value in determining signature of each MS subtype.

Linda in the US asks: Can you please explain about disease progression regarding MRIs of brain lesions versus spinal cord lesions in determining progression?

In patients with progressive disability, especially physical disability, usually spinal cord is involved, sometimes more than the brain. Lesions in the brain may disrupt normal wiring of the brain, which has an important role in cognitive functioning. Therefore it is expected to see more brain changes on MRI in patients with cognitive complaints.

Karen, from Canada says: I would like to hear about how you can predict cognitive decline with MRI scans.

MRI is increasingly used to explain cognitive problems. Tissue loss in brain, and in particular loss of brain cells (known as neurons) are mainly responsible for this. However in the ongoing project we try to explain disease progression in parallel to clinical progression only (mainly physical disability assessed by neurologist). We hope to gather more MRI data with cognitive assessments for future projects.

Alison is asking: You say that the MRI provides an objective assessment of the brain, but I am interested to know your thoughts on hidden inflammation, and recent research on this, which is not picked up by an MRI?

You are right that current technologies in MRI may not pick up all the inflammation. This is also very important during the progressive stage of MS, where ongoing inflammation may not appear as lesions on MRI. There are new research papers suggesting that, for example, inflammation could be seen on brain meninges in addition of new contrast agents. However, these newer concepts have yet to be translated into medical practice.

We’ve received many questions about MS progression, for example: ‘Is the rate of symptom progression more or less constant for progressive MS?’; and: ‘If you have had relapsing-remitting MS for decades, what is the likelihood that the disease will become progressive’?

Unfortunately MS is a heterogeneous disease, which means that its course differs among patients even those classified as a single subtype (for example relapsing-remitting or secondary progressive) and this was the main motivation for the current study. The other point is that the course of MS even in one patient tend to be unpredictable. We hope by analysing more than 500 MRI scans from patients with different disease courses (and other studies with genetic data) we might be able to predict disease course at an individual level in future.

Nigel asks via email: What is the value of me knowing my likely rate of progression?

There are lots of new treatments available for MS, and each year we observe new medications for patients. Future course of disease (prognosis) is an important part of decision making for neurologists. If any method can provide a future prediction of disease course it can hugely help care givers to select the best available treatments.

Peter, in the UK: Are you going to be collecting data from people with primary progressive MS?

Although progressive MS has remained in the dark for the past 2 decades, more recent research during the last few years is focusing more on this subtype of MS. For my research, we are including two cohorts of patients with PPMS, and I hope our results will be useful for people with progressive MS as well.

Joanna asks via Facebook: I have secondary progressive MS, is there any research going on?

MSIF is one of the founding members of the International Progressive MS Alliance, a collaboration of 12 MS organisations around the world funding research which we intend will improve our understanding of the disease and remove the barriers to treatment. Have a look here for more information on what we’re doing: www.ProgressiveMSAlliance.org

Massimo asks from Belgium: I have relapsing-remitting MS and have had no relapse in five years, without treatment – does your study includes cases like mine?

Yes. We do include patients with RRMS, and also patients who have had less symptoms at the beginning of their disease (for example clinically isolated syndrome), with more than 10 years of follow up for these patients.

Elizabeth, from the US asks: Does MS progress faster for African-Americans? Will this research target people of colour and give physicians the knowledge to slow the progression of the disease?

African-American patients have a higher number of relapses with a more progressive course, which underlines the role of genetic factors to define the course of MS. My current project does not look at genetic factors. However, the role of genetic factors is increasingly recognised and will be the subject of our future research.

Rosario, from Argentina: Do you use a specific type of MRI scanner for your research? How could your research be compared to MRI scanners in other countries, taking into account different technologies?

The variability in MRI technologies is an important factor to take into account, especially because over time with the advancement of technology they could produce images with different qualities, and may reduce the reliability of acquired scans when compared to previous ones. We are including hundreds of patients from different MRI scanners from around Europe including London, Amsterdam, Siena and Rome, which we believe will increase the generalisability of our results.

Marianthy asks: Do you believe that the more Teslas an MRI scanner has, the more accurate the results will be?

Higher MRI fields (or higher Teslas as you mention) usually provide more details on the MRI scans. However, because of technical difficulties and lack of availability in some countries this might not be practical.

Eric says: I have read that there is a new MRI machine with a stronger magnet that can see grey matter as well as white matter in the brain. How soon before this grey matter imaging is widely available ?

There are new techniques (also known as MRI sequences) that can show lesions in the brain. One of them is called Double Inversion Recovery. Neurologists use this MRI technique to distinguish MS and other similar disorders, and we know that this might be related to disability. The research in different MRI technologies introduces new sequences constantly. However, it takes a longer time for these new sequences to be validated for everyday clinical use. Whether or not MS starts from grey matter is a subject of great controversy. So far we know that grey matter involvement plays an important role to determine progression and course of the disease.

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