Damaged Brains - The Quest of Austrian MRI Scientist Alexander Rauscher
Dr. Alexander Rauscher - Source: ubc.ca
The Result of Randomness
Rauscher has also been in the news recently, in a most pleasant way, having been awarded the Canada Research Chair (CRC) Tier II in Developmental Neuroimaging. Rauscher’s award, one of 11 new CRC awards at UBC in 2015, provides $500,000 for five years. It can be continued for an additional five years and includes a faculty appointment in UBC’s Department of Pediatrics and the Child and Family Research Institute.
Rauscher’s life has been eventful since moving to Canada in 2007. “I didn’t expect to be an independent scientist when I came here,” he says. His initial position at UBC’s MRI Research Centre was as a research associate. “The thing is that I managed to get a grant, and so normally you have to have an assistant professor position to apply for grants. Out of luck, I found that the Parkinson Society Canada didn’t care whether I was an assistant professor or not, and I got this pilot grant.”
Working with a “very talented” student led to two good publications and “then I was able to convince people here maybe we should change the trajectory from research associate into assistant professor,” effective in November 2010. More awards followed: In June 2012 Rauscher received the Canadian Institutes of Health Research (CIHR) New Investigator Award, and in April 2013 the London Drugs Award for Radiology Research Excellence.
“We were lucky,” he says with disarming modesty. “I can’t give any advice because it is the result of randomness!”
Actually, Rauscher’s whole career trajectory looks a bit random – well-laced with good luck – yet everything contributed to the outcomes, much like his research: “I try different things, and somehow everything is connected in a way.” It’s oddly appropriate that the spins of protons are also random, until the magnetic resonance imaging (MRI) device forces them to align parallel to the direction of its strong magnetic field.
Right People, Right Time, Right Place
Alex Rauscher was born in 1972 in Salzburg, attended Salzburger Bundesgymnasium 2 (now Christian Doppler Gymnasium) and, according to his own account, was not a natural scholar. His parents were passionate about the outdoors, back-country skiing, and rock climbing. So in the 1980s, when most kids got their first computers, “I hadn’t any of that stuff. I always got backcountry skis or such things,” Rauscher remembers. His parents got him his first pair of skis at age three, and took him ski touring at age six. “Until I actually started my master’s degree, I never owned a computer, which is late for a physicist but I wasn’t really interested.”
Nevertheless, good teaching at the Gymnasium had awakened his interest in physics. After graduation, he headed for the Vienna University of Technology and did his master’s thesis with MRI people there. “It was just totally random – I was looking for a project for a thesis and surfed the internet for possibilities and I saw MRI and it looked interesting. So I visited those people. That’s how I got into the field. And I was lucky from then on, plus ending up with the right people, right time.”
Rauscher began his doctoral studies at the Vienna University of Technology, but received an attractive offer from Friedrich Schiller University in Jena, Germany. After working in research for 2½ years, he completed a PhD in engineering physics from TU (2005), then spent another 1½ years in Jena as a post-doc. In 2007 came the opening for a research associate at UBC’s MRI Research Centre, which studied multiple sclerosis, Parkinson disease, and other neuropathologies. For him, and for his long-term Canadian girlfriend, this looked like an optimal environment.
Magnetic Resonance Imaging (MRI) might well be called Nuclear Magnetic Resonance (NMR) Imaging, because it uses principles of NMR to form images. However, doctors felt the word “Nuclear” might scare patients away from this painless, non-invasive, low-risk technique – so the MRI acronym became the norm.
“Everything in an MRI is based on the fact that protons have a spin,” says Rauscher. The magnetic properties of protons – specifically, protons in the two hydrogen atoms of water molecules – cause them to align when a magnetic field is imposed. Not only do protons align their spins, but “how often they go around per second depends on the field strength,” Rauscher explained.
While patients are in an MRI device, their proton spins align parallel (or anti-parallel) to the magnetic field. Radio frequency (RF) pulses are then turned on and off, disturbing the protons’ alignment: They fall out of alignment when the RF pulse turns on and return to alignment when it turns off. MRI signals resulting from these disturbances are strongest immediately after the radio frequency pulse turns off, then decay with time. Originally, MRIs obtained imaging data from signal strength, but today, changes in signal phase also provide important information.
Myelinated axon in rat brain - Source: The Journal of Cell Biology
MRI depends on the fact that these signals may decay at different rates, due to the water’s environment. “Water is somewhat trapped between the lipid bilayers [of myelin], so it has different MRI properties than water that is in intra- or extra-cellular space or in the cerebrospinal fluid,” explained Rauscher. The motion of the trapped water is restricted, and “whenever water molecules are restricted in motion, their signal decays faster than free water.”
Many neurological disorders involve myelin, the lipid bilayers surrounding nerve processes like layers of insulation. For example, in multiple sclerosis, myelin is attacked by the patient’s own immune system. With computers, MRI signals can be used to assess myelin by indicating what proportion of water contributes to the fast-decaying signal associated with myelin (the myelin water fraction) compared to the slow-decaying signal from water in less restrictive intra- or extracellular spaces.
Concussion: The Hardware Still Has Some Issues
“Myelin scanning would not have been an option when we started looking at concussions,” said Rauscher. There was a slow scan that could be used for MS research, and once damaged areas were found, a slice of the scan (about 5 mm thick) could be put into the scanner for quantitative measurements. But concussions weren’t supposed to involve structural damage: no hemorrhage or bleeds in the brain show with conventional MRI. Rauscher’s group needed a scan that could explore the whole brain for damage. “Luckily, we ended up developing a whole brain scan in time for the concussion study, so we added it.”
In February 2016, their concussion studies were published in the peer-reviewed open-access journals PLOS One and Frontiers in Neurology. By early March, they were receiving lots of media attention. The studies used MRI to track a group of 40 male and female ice hockey players, estimating that 8 to 15 were likely to get concussions during the hockey season. But human studies can be challenging, even with a high-risk group: “We only had 11 concussed, but we had pre-injury data, which was very cool,” said Rauscher, and “of course we wouldn’t get ethics [approval] to hit someone on the head!”
Areas of significantly reduced myelin in athletes with concussion, 2 weeks post- injury. - Source: The Vancouver Sun
Their scans looked at hemorrhages, brain volume, white matter, and the myelin water fraction. Athletes who got concussions received additional MRI scans and testing 3 days, 2 weeks, and 2 months after their injury. By the end of hockey season, the brain volumes of all hockey players had decreased slightly compared to controls, whether or not they had experienced concussions. The myelin water fraction had also decreased 2 weeks after a concussion, compared to pre-season scans, but returned to its initial values by 2 months post-injury.
“Sometime between 2 weeks and 2 months the recovery happens,” said Rauscher. “On the average, people say that 10 to 14 days after concussion someone can go back to normal activity, but our data suggest it might be more like 3 weeks – or maybe there’s a gap between the functional recovery … and the actual structural recovery of the specific area that got damaged. …The brains’ software has got back to normal, but its hardware still has some issues.”
In a country of avid ice hockey fans, this was big news. And another “random” success for Rauscher – who hadn’t expected to be an independent scientist when he came to UBC!
“From what I’m doing here with my team, a lot of the stuff – basically, all of it – is creativity. When I look at the past I-don’t-know-how-many publications, none of them were actually in a grant application or funded through a planned grant that I had applied for,” says Rauscher. “It’s all stuff that no funding agency has ever agreed to fund, either because they didn’t like it or because it wasn’t even a grant application. We just had an idea and we tried it and it worked! And of course, there were a lot of things that didn’t work.”
Rauscher plans to use MRI for brain scans of pre-term or term infants with brain injuries, to determine the effectiveness of early interventions. “If you see damage in the brain, and if you see the resolution of damage in the brain based on a certain drug or intervention, we can measure that right away and then … accelerate any clinical trial of new interventions. We don’t have to wait three years for a clinical outcome.”
He is also involved in studies and clinical trials with MS, and sometimes adds a type of MRI scan that might detect something measurable. “There is room for a few minutes of extra scanning of MRI in patients, based on my vague description of what I think it might tell us. No funding agency would give me money, but these are already funded and organized, and all the expensive recruitment and clinical testing are basically covered. All I need to do is add a scan and then find funding to pay students to do some analysis and try out new things. A lot of our work is based on that approach. I’m lucky that I’m in an environment where I can do this!”
“Luck” again … a thread that runs through Rauscher’s scientific career – along with randomness, and creativity, and lots of hard work.
Source: Dr. Alexander Rauscher
Now in his mid-40s, he continues to pursue his passion for back-country skiing, not in the Austrian Alps but in the mountains of British Columbia. Judging by his pictures of the remote snow-covered peaks, this isn’t a sport for the unprepared. But the positive outlook of this newly awarded Canada Research Chair energizes his skiing as well as his lab: “I’m lucky that I’m in an environment where I can do this!”