PET imaging of neuroinflammation in mild traumatic brain injury

Mild Traumatic Brain Injury (mTBI) represents approximately 85% of the hospital
admissions for traumatic brain injury, which make it the most common
neurological disorder generated by external trauma. Almost all mTBI patients
(86%) report one or more symptoms the day after the injury, and 15% of them
still report symptoms after a year. These cognitive disturbances have a major
impact on their lives, e.g. return to work and/or not able to participate in
social activities. The reason for the persistence of symptoms may be an
inflammatory process in the brain in response to the injury. This inflammation
can pass unnoticed by standard imaging techniques, such as computed tomography
(CT) and structural magnetic resonance imaging (MRI), but may be visualized by
Positron Emission Tomography.

The primary objective of this study is to determine if neuroinflammation is
present in patients with mild traumatic brain injury, using [11C]-PK11195 PET.
The secondary objective is to determine if there is a correlation between
[11C]-PK11195 binding and the degree of cognitive deficits, white matter
integrity and serum proteins indicative of inflammation.

This is a observational, cross-sectional study, designed to identify if
neuroinflammation is present in patients with mTBI. Such patients will be
recruited by the Neurology Department of the University Medical Center
Groningen 4 to 6 weeks after the injury, during the follow-up. Patients, that
still have complaints at that time, will be asked by their neurologist to
participate in the study. Healthy volunteers will be recruited via
advertisement in public buildings and local newspapers. Interested subjects
will be approached by the researchers and will receive both oral and written
information about the study. Subjects will have two weeks time for reflection
to decide whether or not to participate in the study. Those that volunteer to
participate are asked to sign the written informed consent and it will be
determined if they meet the inclusion and exclusion criteria.
Patients with continuing complaints 4 to 6 weeks, after the accident, will
undergo a structural MRI and neuropsychological tests, as part of the normal
follow-up procedure. Patients will undergo extra neuropsychological tests if
specific tests are not part of the normal follow-up procedure. At this point
subjects with abnormalities in the MRI, or with underachievement or depression
results during the neuropsychological test will be excluded from the study.
Those patients that surpass all the exclusion criteria will be scheduled for
PET and MRI scans within 8 to 12 weeks after the injury, with a maximum of one
week between the PET and MRI scan. During the PET scan, blood samples will be
taken, to measure serum markers of inflammation.
From healthy volunteers that are willing to participate a blood sample will be
taken to determine C-reactive protein (CRP) and will also undergo the same
neuropsychological tests. Those subjects with serum values of CRP above 10mg/L
will be excluded from the study. In addition, subjects that show
underachievement or depression during the neuropsychological tests will also be
excluded. The remaining volunteers will undergo PET and MRI scans, with a
maximum of one-week interval. Blood samples will also be taken during PET scan.

The subjects have to fill in a questionnaire and undergo neuropsychological
tests, a MRI scan and a PET scan. A total of 170 ml of blood will be taken for
determination of serum markers of inflammation and for PET scan data-analysis.
For the PET scan, the arterial catheterization can cause discomfort and the
subjects are exposed to radioactivity with minor to moderate risk. The patients
will not obtain direct benefit from the study but, if positive results are
obtained, it may lead to new therapies and diagnosis techniques for mTBI.