Dr. Pejman Jabehdar Maralani; Lecturer, Staff Neuroradiologist, Medical Imaging, University of Toronto, Sunnybrook Health Sciences Centre
Project Title: “Quantitative blood oxygenation level dependent (qBOLD) MR imaging of glioblastoma multiforme for assessment of tumour 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 approximately 15 months.
Tumour 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 regions of the tumour are associated with higher rates of progression and recurrence. In this study we will use advanced MRI techniques to non-invasively measure oxygenation in GBM. We take advantage of physical characteristics of Ferumoxytol 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 a 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.
To date, our study has 2 active sites, and we have recruited and screened 5 patients: 4 from Sunnybrook and 1 from SMH. Of those patients, we successfully enrolled 4 and omitted 1 due to ineligibility. We anticipate a sample size of 27 participants.
Preliminary data of the 4 patients screened so far supports the use of our qBOLD technique in accurately and non-invasively identifying hypoxic regions in GBM, which could be used for personalized and targeted treatment. We continue to be hopeful that this technique will lead to better patient outcomes compared to the standard therapeutic techniques currently in place.
Hypoxia is defined as a state of low oxygen in a tissue. In tumours, a hypoxic state is associated with increased aggressiveness and resistance to chemotherapy treatment. This is particularly evident in glioblastoma (GBM), the most common brain cancer in adults and one of the most lethal, with an average survival of less than 15 months after diagnosis. Treatment centres around a combination of aggressive surgical resection, chemotherapy, and radiation.
Currently, the most common technique of detecting hypoxia is with positron emission tomography (PET), but this method suffers from low signal-to-noise ratio, limited availability, and high cost. Our project is aimed at providing a quantitative, non-invasive way of determining oxygenation status in the tumour that bypasses these limitations with magnetic resonance imaging (MRI). With our proposed technique, surgeons can use aggressive surgical methods or radiation oncologists can deliver more focal intensified radiation to specific hypoxic regions in the effect to prolong and improve the lives of GBM patients.
This proposed MRI method utilizes a technique known as “quantitative blood oxygenation level dependent (qBOLD)” imaging to detect tumour oxygenation status. Previous iterations of qBOLD imaging has shown to be effective in rats; one study was even performed in humans with positive results. However, this study utilizes newer and more accurate approaches with two additional means of validating the technique in GBM patients.
We have successfully performed this technique on 10 patients. Our results show that there is a high correlation between qBOLD imaging, and intraoperative as well as pathological findings of hypoxia. Although further studies are required, this suggests that the qBOLD technique can act as a surrogate in the detection of tumour hypoxia.
Hypoxia Detection in Infiltrative Astrocytoma: Ferumoxytol-based Quantitative BOLD MRI with Intraoperative and Histologic Validation
Pejman Jabehdar Maralani, Sunit Das, Todd Mainprize, Nicolas Phan, Aditya Bharatha, Julia Keith, David G. Munoz, Arjun Sahgal, Sean Symons, Sarah Ironside, Zahra Faraji-Dana, Armin Eilaghi, Aimee Chan, Paula Alcaide-Leon, Omid Shearkhani, Raphael Jakubovic, Eshetu G. Atenafu, Greg Zaharchuk, David Mikulis