SIMBA study: Seven Tesla Imaging Biomarkers of Cognitive Outcomes after Treatment for Pediatric Brain Tumor

Treatment advances have increased survival rates for children with brain
tumors. However, many survivors experience neurocognitive problems after
treatment that significantly impact their quality of life and unfortunately
there are few evidence-based interventions to improve cognitive deficits after
they occur. These impairments are most prominent for children who were treated
at a younger age or with cranial radiation therapy (RT), and thus, methods to
prevent RT-related damage are an ongoing field of research.

There is increasing evidence that the early neurobiological changes that occur
after brain tumor treatment are predictive of cognitive functioning in the long
term. In this manner, assessment of changes in the brain may provide a marker
of vulnerability for future cognitive dysfunction, although knowledge of early
and sensitive biomarkers of cognitive decline is limited in children with brain
tumors. Therefore, these results indicate that there is a critical need to
identify early (bio)markers of neurocognitive decline, so that potential
preventative strategies can be implemented prior to the onset of impairments.

This study addresses this knowledge gap by using newly developed, high field
7Tesla (T) Magnetic Resonance Imaging (MRI) techniques measuring vascular
health, metabolism, and diffusion in the brain. Previous research has shown
that 7T MRI can visualize brain structure and function in an unprecedented
manner, including vascular lesions with resolutions of <1mm and brain
pulsatility and metabolism in patients across the age range. Also, small vessel
degeneration and low glutamate levels assessed with 7T MRI have previously been
associated with worse cognitive performance in adult and pediatric populations.
Furthermore, 7T MRI methods have been developed to assess microinfarcts in
neurodegenerative diseases, which were then subsequently applied to 3T MRI
scanners used in the clinic. These results suggest that 7T MRI techniques can
detect brain structural or functional changes in a highly sensitive manner,
which can then be applied to clinical settings. These techniques could be
developed as an early predictive tool for cognitive deficits, although this has
not yet been established for children with brain tumors. Results from the
current study will inform future longitudinal research examining whether
changes in brain vasculature, metabolism, and diffusion precede or accelerate
cognitive decline over time. Ultimately, knowledge from this research can be
used to direct treatment and prevent cognitive decline in pediatric brain
tumor.

The primary objective is to examine relationships between neurocognitive
performance and MRI parameters of brain vasculature, metabolism, and white
matter diffusion in children who have been treated for posterior fossa tumor.
Secondary objectives are to examine relationships between RT dose distribution
and neurocognitive outcomes and to evaluate whether the combination of multiple
imaging modalities can distinguish between survivors who had relatively better
versus poorer neurocognitive functioning.

Single center observational pilot study

Participants will come to the research facility at University Medical Center
Utrecht (UMCU) to complete MR imaging at 7T (1 hr) and to the Princess Máxima
Center to complete neuropsychological testing (2 hr). These appointments will
be completed on the same day when possible. MRI is a non-invasive imaging
modality, involving high magnetic fields, which in general is not associated
with adverse events other than possible claustrophobia due to lying in the
small MR bore. Additionally, some patients may experience some dizziness or
nausea. All participants will already have an MRI during normal clinical
routine; therefore, we can exclude patients with severe claustrophobia.
Patients and parents/caregivers will also be asked to complete
neuropsychological tests and questionnaires. Some patients will complete these
tests as part of standard care, which therefore minimizes time burden.
Furthermore, appointments will be combined with regularly scheduled
appointments as much as possible, and there will be opportunities for breaks if
needed. Most questionnaires can be completed at home through the secure online
KLIK portal. There are no anticipated risks for participation. One potential
benefit is that parents will receive a summary of results from the assessments
(and will be referred for services when needed). Otherwise, there are no
direct benefits for participation and results will be used to optimize care for
future patients.