qBOLD MRI of Glioblastoma Multiforme for Assessment of Tumor Hypoxia.
qBOLD MRI of Glioblastoma Multiforme for Assessment of Tumor Hypoxia.
Glioblastoma multiforme (GBM) is the most common primary malignant brain neoplasm in adults.
 Despite recent diagnostic and therapeutic advances, including aggressive surgical resection
 and chemoradiation, the prognosis of GBM has improved only slightly over the past two
 decades, with median survival of approximately 15 months. Tumor hypoxia is a feature of GBM
 that contributes to poor outcome through multiple mechanisms such as 1) overexpression of
 enzymes that play roles in temozolomide resistance, the main chemotherapeutic agent in GBM
 and 2) increase expression of cancer stem cells which are more resistant to radiation.
 Hypoxic tumour regions are associated with higher rates of progression and recurrence.

 In this study the investigators will use an advanced MRI technique called qBOLD to
 non-invasively measure oxygenation in GBM and obtain targeted biopsies. The investigators
 take advantage of physical characteristics of Ferumoxytol (Feraheme®) which is an iron
 supplement, and utilize two recent technical advances not previously used in human tumours to
 quantitatively measure oxygenation in GBM.

 Prior knowledge of hypoxia can assist in prognostication and individualization of treatment
 planning with special focus on hypoxic regions by targeted radiation dose or regimen
 modulation; consideration of more intensive chemotherapy regimens; more aggressive and
 targeted surgical resection and closer short-term clinical and imaging follow-ups.
We propose a study to demonstrate quantitative oxygen saturation estimation in GBM is
 feasible with qBOLD and it correlates with established histopathological markers of hypoxia
 and angiogenesis, and targeted intraoperative oxygen measurement.

 All patients will undergo surgery as part of their standard treatment. By coregistering the
 hypoxia map on presurgical MRI we will be able to do the following:

 1. Obtain targeted biopsies of the hypoxic areas and none hypoxic areas and correlate them
 with gold standard marker of tissue hypoxia by immunohistochemistry for hypoxia induced
 factor-1α (HIF-1α).

 2. Draw Volumes of interests (VOI) over areas >0.5-cm3 (amenable to accurate
 intra-operative O2 measurement) with the lowest and highest oxygen saturation (SO2)
 values. VOIs will be then imported into the neuronavigation system (Stryker) for
 targeted placement of clinically approved Licox® oxygen-sensing probe (Integra
 NeuroSciences).
Inclusion Criteria:

 1. Adult (>18 year old) patients with newly diagnosed GBM presenting to our centre for
 surgical management and post-operative chemoradiation

 2. Creatinine clearance > 60 ml/minute

 3. Able to tolerate an MR scan

 4. Capable of providing informed consent.

 Exclusion Criteria:

 1. Prior brain surgery or radiation

 2. History of liver disease requiring liver MRI (due to accumulation of ferumoxytol in
 Kupffer cells which can affect liver MRI for up to 3 months)

 3. On more than two antihypertensive medications

 4. History of allergy or adverse reaction to iron supplements

 5. Prior treatment with ferumoxytol

 6. Large (>50%) hemorrhagic component in the solid enhancing part of the tumor

 7. Need for emergency craniotomy.

 8. Pregnant patients

 9. Breast feeding

 10. Serum ferritin of >800 ng/mL