Powerful software reveals brain superhighway ‘tracts’ for surgery and research

Our brains work a bit like highly advanced supercomputers, with bundles of white matter, known as ‘tracts,’ acting as superhighways that facilitate information flow and enable various brain functions. Injuries and disturbances in these tracts are linked to numerous neurological and psychiatric disorders.

However, imaging these white matter tracts is challenging. These tracts are made up of bundles of axonal nerve fibres that are each about 100 times thinner than a human hair. Until the introduction of diffusion MRI, white matter tracts could not be visualised using any other brain imaging technique.

Enter MRtrix3: a sophisticated software package that takes diffusion MRI data, processes those images, digitally reconstructs the brain’s white matter connections, and enables a range of sophisticated analyses of those data. This allows researchers and neurosurgeons to:

• study normal brain development
• improve understanding of neurological diseases like Alzheimer’s Disease, dementias, multiple sclerosis, epilepsy, stroke, traumatic brain injury, and schizophrenia
• plan neurosurgical procedures with greater precision and safety
• perform higher-risk surgeries with improved outcomes

Lead software developer Dr Jacques-Donald Tournier explains, “From the diffusion MRI data we can determine the direction of the white matter fibres at specific points in space and track them through the brain to visualise white matter pathways, which are critical for brain function.”

“You can have brains that look very similar in shape and size, yet function very differently in different people. Some may have problems while others don’t, and we are trying to figure out what’s different biologically,” explains Dr Tournier.

“Sometimes, an MRI doesn’t show any obvious structural differences. But using these advanced techniques, we can detect that while the brain’s surface might look normal, the pattern and strength of the nerve fibre connections to that area are different.”

Before MRtrix3, systems that used tractography to guide surgeries relied on methods pioneered 30 years ago.

But those methods, for many surgeries, would fail to fully capture the complex anatomy of the brain connections, particularly some of the largest and most important white matter tracts in the brain – with potentially huge impacts in the form of deficits in patients after neurosurgery.

“Surgeons use this technology to look at the white matter pathways, and plan their surgery accordingly to avoid damage,” says Dr Tournier.

Dr Joseph Yuan-Mou Yang, Lead clinician scientist (Neuroscience Advanced Clinical Imaging Service, Royal Children’s Hospital) and his team regularly use MRtrix3 software to process, analyse and visualise complex brain scan and tractography images for about 100 children undergoing epilepsy and brain tumour surgeries each year.

“We use tractography generated from MRtrix3 to plan surgeries and guide resections to make surgery more precise and safer,” Dr Yang says. “This is especially crucial for complex surgical cases.”

“It has allowed neurosurgeons to carry out surgery in cases that might have been seen as too risky or impossible before.”

MRtrix3 uses image processing and digital reconstruction algorithms to look at white matter fibres three orders of magnitude smaller than the resolution of the images. Any quantitative measurements of the white matter must be carefully tailored to the “funky geometry” (as co-developer Dr Robert Smith describes it) of the underlying biological structures.

It facilitates very fast computation of the complex image analysis problems involved to provide functional, robust and biologically meaningful insights.

Dr Tournier describes his surprise at the variety of applications MRtrix3 is used for: “At our last workshop, this guy caught me and says, ‘I’m trying to reorient this image here; it’s a bit off. This is an aardvark brain’.” MRtrix3 is not only being applied to humans, and indeed not only to brain imaging data.

MRtrix3 has helped improve outcomes for Alzheimer’s disease patients. “All the early papers on Alzheimer’s showed effects in the frontal and temporal left side regions, but not all in the same study,” says Dr Tournier. “But when we ran our software, it really pulled out those effects, which was very exciting at the time.”

Dr Yang notes that his team has used MRtrix3 with other research imaging tools for various white matter connectivity research studies examining disorders such as paediatric epilepsy, brain tumours, stroke, ADHD, traumatic brain injury and more.

Sophisticated, free, and open source, MRtrix3 also has a lively user forum that the developers Dr Tournier and Dr Smith exhaustively support – with over 1,800 users and 7,500 discussion threads.

On the open-source angle, Dr Tournier is clear about its benefits: “It works well for us to be open source, if you want to have widespread adoption. The thing that really matters to us is to have impact and demonstrate impact.”

“At the start [early 2000s], it was very nerve wracking to put our code, with all its bugs, up on the internet,” he says. “But over the years, it has really engendered trust. We have all these processes in place; everything gets tested and reviewed. It feels good to contribute and see collaborations that have resulted from it.”

Dr Smith is proud of those contributions, too: “We have this desire to be providing software that is robust, that is validated. And we’ve created something that is hopefully going to enhance the capabilities and the quality of other people’s research.”

MRtrix3 is supported by the Australian National Imaging Facility, The Florey, King’s College London, KU Leuven and University of Antwerp to improve health outcomes on a global scale.