Saturday, October 04, 2014

Ride Ataxia funded research. MRI biomarker study at UMN

Each year FARA puts out a request for proposal for research to be funded by funds from Ride Ataxia. This research grant is focused on translational research - research that will help bridge the gap between the laboratory and the clinic. Last year the Ride Ataxia named award went to a team at the University of Minnesota who is analyzing the anatomical and functional connectivity of the central nervous system in FA using Magnetic Resonance Imaging (MRI). This work is critical to understanding when and which neurological pathways are compromised in FA and will be a building block for future therapies.  The Bob Allison Ataxia Research Center (BAARC) also contributed to the funding of this initial grant.

In July 2013, I took a trip up to Minneapolis to meet the research team and contribute to the project by offering images of my spinal cord. The first scan was on Monday and I arrived CMRR (Center for Magnetic Resonance Research) mid-morning for my baseline exam which included the usual touching finger to nose, tuning fork to toe, and peg board test among others.  That's when I had my first in-person contact with the team at UMN.  I had been working with Diane Hutter for months planning my travel, accommodations, and schedule for my visit.  Diane put me through the paces of the FARS (Friedreich's Ataxia Rating Scale) and put me at ease as we prepared for 5 hours in 2 days in the "the magnet".  Diane, thank you for your hospitality and friendship.

Then I prepared to get inside the magnet for the first time.  The CMRR has quite a few magnets.  Most MRI machines at hospitals are 1.5 T (representing the power of the magnet and the resolution of the images that can be produced).  This study uses 3 T and 7 T magnets. The CMRR has a 9.4 T magnets and they are building a 10.5 T magnet which will be the strongest in the world.  It was clear to me that this was the place to be for an MRI study.

When you go into the room with the magnet there are signs everywhere that say "NO METAL IN THIS ROOM" so the preparation includes changing into scrubs and leaving everything in the locker in the prep room.  They even ask if you have any tattoos because there is iron in the red and orange colors that could be a problem in the magnet, it's crazy strong!  I layed down on the table and the team covered me in all kinds of equipment to collect data from the machine and then covered all of that with a blanket because they keep it nice and cool in that room.

The first scan took an image of my spinal cord from my brain all the way down to my lower back.  It is a composite image of a bunch of different images of different sections of my spine so the bed was moving back and forth as I laid on my back with the tube about 6 inches from my nose while the machine made all sorts of loud buzzing and hammering noises (I had earplugs in and music playing through headphones and I could talk to Dr. Jim Joers [the man at the controls] whenever I wanted.  Plus I had this little squeeze ball in my hand that I could squeeze to let the team know if I was getting uncomfortable).
This image is not the final product.  After the image is captured, Dr. Christophe Lenglet takes over and applies two masters degrees in Computer Science and Engineering, and Applied Mathematics as well as a PHD in Biomedical Imaging & Neuroscience plus a few years experience as a research scientist for Siemens (the company that makes the MRI machines) to create a 3D rendering of the spinal cord so they can better understand the structural and functional alterations of brain connections in FA.

Dr. Lenglet's TEDx Talk:

These images are not the only thing that comes out of this study.  A super specialized technique called Spectroscopy looks at a very specific part of the spinal cord and measures the concentration of certain chemicals in that particular spot.  This study takes a look at people with FA and compares their MRI’s to age matched controls who do not have FA.  The difference in the concentration of these certain chemicals between people who have FA and people who do not have FA will help tell the story of the effects of the disease.  These differences will hopefully let the researchers measure very accurately, the progression of the disease and will help us determine if a drug is working when this technique is used in a clinical trial because it will help tell if the drug has altered the course of FA.

The area that the researchers target for spectroscopy in the spinal cord is a very small section (6mm x 8mm x 30mm) so the scan is very sensitive to movement.  I kept falling asleep during the spectroscopy portion of the scan – and when I fall asleep, I twitch, which was not helping the data collection process.  I can hear Dr. Joers in the little ear plugs, and he can hear me talk back, so he very politely told me that the movements were not great for the data and then I stayed awake for the final 20 minutes.  I am going to pick a different Pandora station next time, Jack Johnson was putting me to sleep.  Perhaps I need to go with some punk rock from my highschool/college years.

In the end Dr. Jim Joers and Dr. Pierre-Gilles Henry said they got the data they needed and it looked good.  After the data is collected, Dr. Henry applies his expertise to analyze the spectroscopy data.

Dr Henry has two Masters degrees: one in Electrical Engineering from SUPELEC in Paris, France, and one in Neuroscience from University of Paris 6.  He got his PhD in Neuroscience from the University of Paris 6 in 2000 and then came to the CMRR in Minneapolis. From 2001 to 2010, he did fundamental research on developing new methods to study brain metabolism using MR spectroscopy (MRS).

From Dr Henry: "MRS is really a unique technique that allow us to study the neurochemistry and metabolism of the nervous system non-invasively.

In 2010, after a major life change (cochlear implant surgeries), I decided I wanted my research to have a more direct impact on the life of patients. I am now focusing my efforts on two diseases: Huntington's Disease and Friedreich's Ataxia. The main goal, as you know, is to find good biomarkers for clinical trials."

Top left: Dr. Jim Joers. Top right: Dr. Pierre-Gilles Henry. Bottom left: Dr. Christophe Lenglet. Not pictured: Diane Hutter.
With the data that they collected and analyzed over the past year, the team was able to prove that there is measurable damage to the nervous system in people with FA and they were able to get another round of funding from FARA, GoFar, and Ataxia UK to scan more patients in hopes of finding out how damage to the nervous system changes over time.

Another aim of this study is to figure out what the timeline looks like for damage to the nervous system and how severe the damage is when correlated with the neurological symptoms (balance and coordination) of the disease.  They still need subjects who are in early stages of the disease and pre-symptomatic patients who would like to accelerate research with their participation.

I am always excited to participate in research that will get us closer to a treatment and a cure for FA.  Ride Ataxia provides an opportunity to contribute to the research that will get us there.

See you on the road!

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