3T MRI Biomarkers of Glioma Treatment Response

PRIMARY OBJECTIVES:

I. To correlate treatment-induced changes in quantitative MRI-based biomarkers—specifically,
those sensitive to tumor protein content (amide proton transfer asymmetry [APTasym] from
chemical exchange saturation transfer [CEST]), cellularity (apparent diffusion coefficient
[ADC] from diffusion-weighted imaging [DWI]), and blood flow (volume transfer constant
[K^trans] from dynamic contrast-enhanced [DCE]; cerebral blood flow [CBF] from dynamic
susceptibility contrast [DSC])—with treatment-induced changes in tumor size, measured via
standard anatomic MRI.

II. To correlate treatment-induced changes in the above quantitative MRI endpoints with
patient progression-free survival (PFS).

OUTLINE:

Patients undergo measurement of tumor protein content using CEST-MRI, cellularity using
DWI-MRI, and blood flow using DCE-MRI and DSC-MRI within 2 weeks of treatment and at 2 and 4
weeks after initiation of treatment.

Inclusion Criteria:

- Patients must sign an institutional review board (IRB)-approved informed consent
document

- Patients must have been diagnosed with high-grade glioma:

- World Health Organization (WHO) grade III: anaplastic astrocytoma,
oligodendroglioma, ependymoma, or oligoastrocytoma; OR

- WHO grade IV: glioblastoma multiforme; or neuroepithelial tumors of uncertain
origin (polar spongioblastoma, astroblastoma, or gliomatosis cerebri)

- As measured by conventional high spatial resolution MRI, the minimum diameter of the
primary lesion (short axis) should be at least 5 mm

- Patients must be scheduled to receive: 1) standard chemotherapy with/without
radiation therapy; OR 2) single-agent bevacizumab (Avastin)

Exclusion Criteria:

- Patients with low-grade (WHO grade I or II) glioma

- Patients with metastatic disease

- Patients who have any type of bioimplant activated by mechanical, electronic, or
magnetic means (e.g., cochlear implants, pacemakers, neurostimulators,
biostimulators, electronic infusion pumps, etc), because such devices may be
displaced or malfunction

- Patients who have any type of ferromagnetic bioimplant that could potentially be
displaced

- Patients who have cerebral aneurysm clips

- Patients who may have shrapnel imbedded in their bodies (such as from war wounds),
metal workers and machinists (potential for metallic fragments in or near the eyes)

- Patients with inadequate renal function (creatinine >= 1.5 times upper limit of
normal) or acute or chronic renal insufficiency (glomerular filtration rate < 20
ml/min)

- Patients who are pregnant or breast feeding; urine pregnancy test will be performed
on women of child bearing potential

- Patients who exhibit noticeable anxiety and/or claustrophobia or who exhibit severe
vertigo when they are moved into the magnet bore

- Patients incapable of giving informed written consent, for the following reasons:

- Inability to adhere to the experimental protocols for any reason

- Inability to communicate with the research team

- Limited ability to give informed consent due to mental disability, altered
mental status, confusion, cognitive impairment, or psychiatric disorders

- Patients scoring 14.5 or lower on the University of California at San Diego
(UCSD) Brief Assessment of Consent Capacity (UBACC) Capacity to Consent
Questionnaire will be excluded

- Prisoners or other individuals deemed to be susceptible to coercion

- For patients who have undergone surgical resection prior to joining the study, in
whom baseline magnetic resonance (MR) images exhibit enough signal degradation (due
to susceptibility artifact in the region of the surgical bed) such that the data are
uninterpretable will be excluded