Radiation Biology for Physical Scientists/Imaging Tumour Physiology

Functional MRI measuring oxygen concetrations

Tumor Hypoxia

Magnetic Resonance Imaging Based

Oxygenated haemoglobin has different magnetic properties than its de-oxygenated form. These magnetic differences can be detected and imaged using a technique called Blood Oxygen Level Dependent (BOLD) Magnetic Resonance Imaging.BOLD characterization of haemoglobin oxygen saturation can be used to reflect vascular hypoxia but not tissue hypoxia¹.

Dynamic Contrast Enhanced (DCE-MRI) with gadolinium diethylene-triamine penta-acetic acid as the contrast agent can be used to image hypoxic fraction. MRI T1-weighted images are taken before and after an intravenous injection of gadolinium².

Positron Emission Tomography Based

Positron Emission Tomography combined with the hypoxia PET reagent 18F misonidazole³ or 60Cu-ATSM⁴ (copper-60 labeled diacetyl-bis( N(4)-methylthiosemicarbazone))₄.

Optical Based

Optical spectroscopy measures haemoglobin saturation ⁵ which is correlated to vascular hypoxia. This technique is limited to imaging sites that offer optical access.

Interstitial fluid pressure

Dynamic Contrast Enhanced (DCE) Magnetic Resonance Imaging can be used to image the interstitial fluid pressure in tumors using gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA) as the contrast agent.

Metabolism

• Fludeoxyglucose (18F) abbreviated to FDG can be used with Positron Emission Tomography to image tumour metabolism.

• Lactic acid is the product of anaerobic metabolism. Lactic acid metabolism can be measured using hyperpolarized ¹³C-pyruvate.

References

1. Duong TQ. Cerebral blood flow and BOLD fMRI responses to hypoxia in awake and anesthetized rats. Brain research 2007;1135(1):186-194. doi:10.1016/j.brainres.2006.11.097. PMCID 2949962

2. Egeland, T. A.M., Gulliksrud, K., Gaustad, J.-V., Mathiesen, B. and Rofstad, E. K. (2012), Dynamic contrast-enhanced-MRI of tumor hypoxia. Magn Reson Med, 67: 519–530. doi: 10.1002/mrm.23014

3. Yang, David J., et al. "Development of F-18-labeled fluoroerythronitroimidazole as a PET agent for imaging tumor hypoxia." Radiology 194.3 (1995): 795-800.

4. Dehdashti, Farrokh, et al. Assessing tumor hypoxia in cervical cancer by PET with 60Cu-labeled diacetyl-bis (N4-methylthiosemicarbazone). Journal of Nuclear Medicine 49.2 (2008): 201-205.

5. Culver, Joseph P., et al. "Diffuse optical measurement of hemoglobin and cerebral blood flow in rat brain during hypercapnia, hypoxia and cardiac arrest." Oxygen Transport To Tissue XXIII. Springer US, 2003. 293-297.