Deep brain stimulation for Parkinson's Disease: a feasibility study on anatomical, functional and diffusion-weighted MRI

Parkinson's Disease patients suffer from severe motor symptoms. In an early
stage of the disease, the patients are treated with medication. After
long-term treatment however, this medication will often cause even more severe
motor side-effects. For these patients, deep brain stimulation is an
alternative therapy. Deep brain stimulation involves the implantation of
electrodes that stimulate the brain at a high frequency. It is assumed that
this alleviates the motor symptoms due to the inhibition of a hyperactive
nucleus, the nucleus subthalamicus or STN.

The locomotion improves, but in 41% of the cases, cognitive side-effects occur
after the operation. A group of 8% suffers from a depression, while 4% becomes
manic. This can be explained by the fact that the STN does not only have a
motor, but also a cognitive and an emotional function. Studies on monkey and
rat brains have proven that three subparts of the STN can be indicated as well,
that each have their own function.

Our hypothesis is that the cognitive side-effects can be avoided by a more
specific stimulation of the motor part of the STN.

The goal of the entire PhD project is to find the motor part of the STN using
advanced image acquisition and image analysis. To reach this eventual goal, we
first have to be able to visualize the STN as a whole. Published studies show
only 2D-images with often vague contrast, made with just one of the possible
protocols. Thus, our first goal is the verification and comparison of published
protocols in three dimensions. Furthermore, we will investigate new scan
protocols. The results of these experiments can be used immediately for a
better planning and navigation for deep brain stimulation in the hospital.

The second objective is to distinguish the three different subparts of the STN.
We will experiment with diffusion-weighted MRI to analyze the connectivity of
the STN with other brain areas. We assume that the directions of the nerve
tracts in the brain, derived from diffusion-weighted images, can be used for
this purpose, because the different parts of the STN are each connect to
different other areas, depending on the function.

Thirdly, we want to generate complementary information using functional MRI. We
will map both the location of STN activation and the correlation in activation
in the STN and other parts of the brain.

Eventually, the collection of all these data should lead to a more precise
localization of the STN and its motor part preceding a deep brain stimulation
procedure.

This study is just a pilot or feasibility study on the right protocols, using
healthy volunteers.

The burden per subject comprises one visit to the radiology department, lasting
about 80 minutes, of which 30 minutes will be used for introduction and
screening. Afterwards, five scans of in total 50 minutes will be made.

Because a metal screening will be done and no contrast agent will be injected,
there is almost no risk for the subject.

Because of the very low risk and because the subject only sacrifices 80 minutes
of time, the study seems justified, looking at its possible benefit. This
benefit is the avoidance of cognitive side-effects of deep brain stimulation.
Currently, many patients cannot undergo deep brain stimulation, only because
the risk of side-effects is too large.