In this lecture, we will review the current susceptibility imaging methods used for indirectly assessing tumor hypoxia in abdominal cancers, in preclinical and clinical applications. We will review the scientific evidence, potential applications and limitations of BOLD/TOLD imaging.
Susceptibility Imaging in Abdominal Cancers
Intratumoral hypoxia has been shown to correlate with tumor invasiveness, progression and radioresistance in animal models and human cancers. Tumor cells have been shown to adapt to hypoxic stress through genome and proteome changes induced via the HIF 1-α pathway, which promotes tumor progression and malignancy. Moreover, low oxygen content in tumor tissue decreases the effectiveness of radiotherapy and chemotherapy. Tumor oxygenation has been shown to be influenced by several factors including microvessel density, blood flow, blood volume, blood oxygen saturation, tissue pO2 and oxygen consumption rate. Information on oxygen bioavailability in tumors can have important clinical implications, such as stratification of patients for therapy and monitoring response to systemic and locoregional therapy. The development of new imaging techniques, such as oxygen-sensitive MRI makes it possible to determine the perfusion and oxygenation state of tumors non-invasively. MRI techniques such as blood oxygen level dependent (BOLD) and tissue oxygen level dependent (TOLD) were first developed to study areas of activation in the brain, but have since been used for in vivo evaluation of tumor blood supply and oxygenation. In BOLD MRI, deoxygenated hemoglobin (deoxy-Hb) acts as an endogenous contrast agent by increasing magnetic susceptibility and shortening the transverse relaxation time (T2*) of the bulk magnetization of water protons in nearby tissues. In hypoxic tissues, the proportion of deoxy-Hb is greater, so the transverse relaxation rate R2* (1/T2*) is higher, and is expected to decrease during a hyperoxic respiratory challenge, as deoxy-Hb becomes more saturated with oxygen. Studies in rodents and humans have shown BOLD signal increase (R2* decrease) in various tumors, including hepatocellular carcinoma (HCC), in response to breathing 100% O2 or carbogen. Since Hb saturation with O2 is dependent on the arterial O2 pressure and oxygen partial pressure in tissue (pO2), R2* can be thought of as an index of oxygenation. However, since other factors, such as blood volume, flow and vessel geometry affect the concentration of Hb in tissue, R2* cannot be used to infer pO2.1. Semenza GL. Hypoxia and cancer. Cancer Metastasis Rev 2007;26:223-224
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