An ultra-high-resolution model of the brain stem could help better guide neurosurgeons treating conditions such as tremor and Parkinson’s disease with deep brain stimulation (DBS).
In a study published on June 3, 2015, in Human Brain Mapping, scientists at Duke Medicine announced a 3-dimensional (3D) map of the human brain stem with an extremely high level of detail because of the magnetic resonance imaging (MRI) and computing techniques used.
The new 3D model could eliminate risky "trial-and-error" maneuvers as surgeons implant electrodes—a change akin to trading in a paper road atlas for GPS.
“On conventional MRI that we take before surgery, the thalamus looks like a gray mass where you can see only the borders,” says neurosurgeon study author Nandan Lad, MD, PhD, and director of the Duke NeuroOutcomes Center. “Now we will have actual detail. With this map, for the first time we’re able to see the thalamus and that underlying circuitry that we are modulating.”
The map images are thousands of times more detailed than clinical MRI. “You can actually see the nerve fibers in the brain, how they’re crossing, and the subtleties of contrast between gray and white matter in the brain far beyond what a clinical scan could offer,” explains G. Allan Johnson, PhD, study author and director of the Duke Center for In Vivo Microscopy, which is where the brain stem was scanned.
The brain map was produced from a 10-day scan of a brain stem from a healthy deceased donor using a 7-Tesla MRI system and was then converted into a 3D model. Using a high-performance computing cluster, that model can then be proportionally scaled to fit the unique brain anatomy of an individual patient.
Currently, many neurosurgeons rely on lower-resolution computed tomography and MRI scans as well as geographic coordinates relative to the planes of the brain to guide them when placing electrodes in the thalamus. They are targeting a circuit called the dentatorubrothalamic tract (depicted as an X-shaped pathway in the video here), notes Lad.
Oftentimes, surgeons must remove and reinsert electrodes and test frequencies to find the spots inside the thalamus where, for instance, the electric current subdues the hands of a patient with debilitating tremors. This indirect targeting is the standard of care for DBS, but it has risks. Moving an electrode requires another pass through delicate tissue, and complications from DBS can include hemorrhage, seizure, or memory problems.
“This map will potentially help us reach the optimal target the first time,” Lad expounds. “It could eliminate trial and error and make the surgery safer.”
To test the accuracy of the model, the researchers conducted a retrospective study of 12 participants with tremors who had already been successfully treated using DBS. The researchers used the 3D model, which was scaled to fit each individual patient's anatomy, to predict the best placement for the electrodes in each patient. They discovered that the predictive computer model and the actual, successful electrode placements correlated for 22 of 24 electrodes in all of the study participants.
The researchers will soon begin a prospective study using the 3D model to guide DBS surgery.
“As time goes on, imaging will only continue to get better,” Lad explains. “We are well-equipped and at the cutting edge of understanding how to apply this technology, and we will be in an even better position to treat more patients with fewer side effects."
The team at Duke will also pursue high-resolution imaging of other circuits in the brain stem, other areas of the brain, and the spinal cord to develop novel treatments for other conditions.
“We now have a guide to visualize these complex neuronal connections that would otherwise be impossible to see,” notes Evan Calabrese, PhD, the lead author of the paper and the person who engineered the 3D model. “This will help us continue to explore applications for treatments of Alzheimer’s disease, neuropathic pain, depression, and even obsessive compulsive disorder.”
In addition to Johnson, Calabrese, and Lad, study authors include Patrick T. Hickey, DO, Christine M. Hulette, MD, Jingxian Zhang, and Beth Parente, MHS, PA-C.