The Montreal Neurological Institute (MNI) is a research and medical center located in Downtown Montreal, where great physicians, researchers and Engineers from Montreal like Dr. David Rudko, get together for analyzing, training and developing new procedures for treating neurological diseases. The MNI is part of McGill University Health Center, which it is dedicated for neuroscience. At first, it was located in within the establishment of the Royal Victoria Hospital, until it grew and founded their own establishment across the Royal Victoria Hospital location.

 

I was honored to interview Dr David Rudko.  He is an Assistant Professor at McGill University in the Departments of Neurology/Neurosurgery and Biomedical Engineering. He completed his undergraduate studies at University of  British-Columbia in physics. He then earned his Master’s degree in medical physics at the University of Victoria, where he focused on radiation therapy. He then pursued his PHD in high field-MRI at Western University. Later, he came to McGill for his Post Doctorate  with Dr. Douglas Arnold in the MRS imaging group. He became a P.I. 2 years ago and has started his own lab that focused on quantitative microstructure imaging and biophysical modeling. High Field MRI became his main interest during his undergraduate studies, by enjoying physics and biological physics, so by combining both, also by adding other topics that he enjoyed like signal processing, Fourier transforms and etc. , by merging all of these interesting aspects, led him into this field.

 

Overview of Multiple Sclerosis

Multiple sclerosis (MS) is a chronic and inflammatory disease of the central nervous system. It affects approximately 2.5 million people worldwide. It is one of the most common causes of non-traumatic neurological disability in young adults. Magnetic Resonance Imaging (MRI) has been a key tool for detecting, diagnosing, monitoring and treating MS.  Also, MRI has been used for understanding the history, progression and pathophysiology of MS. The article gave us an overview of MS and described the application of multi-surface longitudinal measurements of magnetization transfer ratio (MTR) with a MRI strength field of 3T between MS patients and controlled patients.

Fig 1: Myelination (top) vs Demyelination(bottom)

Interview Questions and Answers

1.      Is  Magnetization Ratio Transfer (MTR) the solution for detecting Multiple Sclerosis(MS)?

Detecting signatures of MS using MRI can be performed in different ways. Some approaches attempt to measure myelination or demyelination in white matter lesions, while others may look at normal appearing white matter. In this paper, we specifically examined cortical gray matter. In the spectrum of many quantitative MRI techniques, magnetization transfer ratio (MTR) is an older technique. It was used here for a longitudinal study with longitudinal mixed model analysis. MTR is an indicator of myelination in cortical gray matter tissue

2.  Old vs New: Is there a newer technique for identifying MS in the Cortical Gray Matter? This led you and your team to new possible ways.

        There is always a tradeoff when applying different quantitative MRI techniques for measuring demyelination .Quantitative MTR serves as a partial gold standard to measure bound proof fraction. However, it is a technique that requires a long acquisition time. Recently, efforts have been made to accelerate qMTR and this may be a future avenue of research. The efficiency and sensitivity of myelin-sensitive MRI is always a function of sensitivity and specificity of particular MRI techniques. When it comes to MS, different techniques will give different effects sizes. An ideal goal, from a research perspective, is to have  a cohort patients ranging between 20 to 40 and see an effect. In such a scenario, you could calculate power in drug studies and can see the effect of a drug on subpial demyelination.

Regarding newer leads to newer techniques, he says: So, there is that ongoing study that uses this multiple field strength to look at the cortical pathology, that is the main one and then we used other contrast like T-1 and R-2 star. I am trying to use that in a laminar pattern. We also been looking at cognition in MS patients, there is a hypothesis that the cortical pathology make correlate with cognitive deficits in MS patients, which is kind of,  cognition is fairly poorly characterized in MS but it is a big effect if you ask an MS patient that they might say one of the leading detriments that they have is that the executive functions process, speed decisions is affected, where particularly in the brain, what is responsible for that is kind of unknown.

3. Outer vs Inner: Why the results appears on the outer cortical surface but not in the inner surface?

The work follows from earlier post-mortem histopathology studies  performed by Alexandra Kultzelnigg in Dr. Hans Lassmann’s lab in 2005. Figure 2 shows  a histological slide of brain tissue. Areas of subpial demyelination are highlighted in orange. There is extensive  gray matter demyelination that may occupy a larger area than the traditional white matter demyelination. We traditionally thinks of MS as a demyelinating disorder with characteristic plaques located around the ventricles. By contrast, in this later stage MS patient, there is cortical pathology indicated by the orange colors in Fig. 2. The orange color shows reduced proteolipid protein density. It is reduced more on the outer layer of the cortex . SP patients appear to show greater extent of sub-pial demyelination.

Fig 2: A. Kutzelnigg paper of orange color on outer cortical surface shows proteolipid protein density, which is a marker of myelin

4. Predicting MS, is it possible? Types for testing MS patients. Is MS geographically focused on a certain group of people?

The MS patient group employed in the study was chosen based on phenotype, age range and educational status. There is more interesting studies that can be done by a larger cohort like genetics to geography, we know that MS is mostly influence by geography. It is a very hard question to answer if there is a way for predicting MS. People would like to use MRI early to find any early biomarker that someone will become MS in the end. There are some studies, there a condition called Clinical Isolated Syndrome (CIS), someone that has a first demyelinating event and maybe an attack. The neurologist might think they have MS, but they can say for certain. There is some MRI studies that use it as biomarker but there is nothing that exist yet. There is administrative therapies that drugs just controls, they don’t cure it. There is experimental drugs on the market that targets the B-cells but nothing is certain. The bread and butter are MS therapies for reduce the inflammation in the brain, but it is a none specific thing.

Dr Rudko added a comment about MS:

One of the problems with the diagnostics imaging for MS, is that there is a lot benine hyperintensities in the brain that just accumulates with age, so the neurologist needs to be certain with what he sees is a lesion, in order to use the MacDonald’s criteria for diagnosing MS. MRI is one of the diagnostic criteria. If a patient has a lesion in two different part of the brain, or, they have different lesions over time in other areas in weeks of month of time, it is sort of indicative of him having MS.

Allman, J.M., Hakeem, A., Erwin, J.M., Nimchinsky, E., Hof, P., 2001. The anterior cingulate cortex. The evolution of an interface between emotion and cognition. Ann. N. Y. Acad. Sci. 935, 107–117.