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“This work might therefore represent a platform for a co-clinical translational project that will contribute to further the use and implementation of new BOLD related methodologies in the study of hypoxia.” Virani, Needa
Hypoxia in tumors is associated with invasive and malignant cancerous characteristics as well as resistance to radiotherapy and chemotherapy procedures. This is due to inadequate oxygen supplies within the cells that are necessary to carry out cell functions, maintain nutrient levels, influence permeability, regulate pH, and prevent invasion. Hypoxia thus increases the production of HIF-α, which in turn increases the production of VEGF, Ang-2, and other factors that promote cell birth as well as CXCR4 and E-cadherin factors needed for cell division.
Different techniques have been utilized in the monitoring of tumor hypoxia including immunohistochemistry (IHC) staining based on biomarkers such as pimonidazole and nitroimidazoles.
However, there is a need for an improved methodology that solves the challenges that arise from invasive IHC and low resolution studies. Researchers are now studying how new methods can sensitively detect and monitor biomarkers of hypoxia like pimonidazole in brain tumor cells.
BOLD MRI stands for Blood Oxygen Level-Dependent MRI and is a functional solution for hypoxia studies which can be conducted in murine models. BOLD MRI is suited to effectively tracking minute oxygen changes in human neurological systems and is thus a fitting technique to assess in examining neural tumor hypoxia.
Is BOLD MRI correlated with pimonidazole measurements of hypoxia?
Pimonidazole binds to proteins in hypoxic cells, making it an ideal marker for hypoxia. BOLD MRI can detect areas of hypoxia tagged with pimonidazole during later developmental stages of tumors. A group of scientists from the United States and Japan published a research paper in the journal Magnetic Resonance Imaging detailing their study of this correlation hypothesis.
The scientists used murine orthotopic glioblastoma models. After imaging and undergoing an oxygen challenge, pimonidazole was injected into the mice, which were euthanized 90 minutes later. Then the brain was sectioned for immunohistochemistry analysis.
The scientists used a Bruker BioSpec 70/30 to conduct the MRI in vivo studies. For brain imaging, a transmit/receiver 23 mm volume radiofrequency (RF) coil from Bruker was utilized. For MRI data acquisition, the scientists employed Paravision 6.0.1.
The data supported a correlation between BOLD MRI and pimonidazole measurements in an entire tumor and confirms this methodology accurately monitors tumor hypoxia regions. The BOLD MRI approach has now recently shown potential in a clinical trial with human lung cancer patients as well.
Further investigation is needed into regions of low and high oxygenation during the oxygen challenge as well as the correlation between locations of hypoxic areas in MRI maps and the IHC staining. Specific intra-tumor spatial information remains elusive and BOLD MRI did display some susceptibility challenges. However, BOLD MRI circumvents many traditional technique challenges and continues to show promise in the realm of tumor development and therapy.
Reference:
Virani, Needa et al. “In vivo hypoxia characterization using blood oxygen level-dependent magnetic resonance imaging in a preclinical glioblastoma mouse model.” Magnetic Resonance Imaging vol. 76 (2021): 52-60. DOI:10.1016/j.mri.2020.11.003