Quantitative Assessment of Radiation-induced Neuroinflammation - A Proof of Principle Study

QARIN 1 is a study of \[18F\]DPA-714 Translocation Protein (TSPO) Positron Emission Tomography (PET) for longitudinal, quantitative assessment of brain neuroinflammation following whole brain radiation therapy. This TSPO PET, uses a radioactive tracer. An optional MRI (magnetic resonance imaging) will also be performed to monitor brain microstructure damages induced by neuroinflammation. Primary Objectives * Assessment of temporal and regional variability of uptake of translocator protein (TSPO) positron emission tomography (PET) tracer. * Regional variability will be assessed in medial temporal lobe, frontal lobe, and in white matter * Temporal variability will be assessed by scanning each subject four-times: at baseline (before or within 2 weeks of start of radiation therapy), before start of chemotherapy, at 1 year from the initiation of the radiation therapy, and at 1.5-2 years from the initiation of the radiation therapy * Correlation of radiation dose in specific brain regions with radiation induced neuroinflammation as measured by uptake of TSPO PET tracer. Exploratory Objectives * Assessment of radiation-induced brain microstructure injuries (RIBMI) in specific brain regions (medial temporal lobe, frontal lobe, and in white matter) using advanced magnetic resonance imaging (MRI) techniques. * Association of radiation dose with MRI measures of RIBMI in these specific brain regions. * Association of PET measures of RIN with MRI measures of RIBMI. * Association of PET measure of RIN and MRI measures of RIBMI in specific regions of interest (ROI) with specific domain of neuro-cognition. For example, to investigate whether PET measure of RIN and MRI measures of RIBMI in hippocampal ROI have strongest association with episodic memory; whether frontal lobe cortical ROI are associated with attention and executive function. * Association of a novel MRI based technique for assessment of RIN with TSPO PET. * Association of the PET and MRI measure of neuroinflammation within 2- years of completion of radiation with delayed cognitive outcome that will be measured at 3, 4 and 5 years from the completion of radiation

Sex

All

Minimum age

8 Years

Maximum age

39 Years

Inclusion Criteria

* Participant is at least 8 years of age
* Participants with histologically confirmed medulloblastoma and are scheduled to receive 36 Gy craniospinal irradiation
* Participant and/or guardian can understand and is willing to sign a written informed consent document according to institutional guidelines
* Subjects have either have high-affinity or mixed-affinity TSPO binding sites as determined by the single-nucleotide polymorphism (SNP) rs6971 in the TSPO gene.

Exclusion Criteria:

* Participants with a large pseudomeningocele (\>4 cm in size) at the surgical site, complications from ventricular access (evidenced by hemorrhage and/or enhancement along the catheter), large subdural effusion in the supra-tentorial compartment (\>1 cm in the maximum transverse dimension). All of these are expected to induce inflammation.
* Female participants of childbearing age must not be lactating due to theoretical potential harm to the infant from exposure to radiation.
* Subjects with low-affinity TSPO binding sites as determined by the single-nucleotide polymorphism (SNP) rs6971 in the TSPO gene.
* Pregnant subjects.
* Patients needing sedation for the PET scans or optional MRI scans.
* Participants with a diagnosis of recurrent medulloblastoma.