An efficient noninvasive method for in vivo imaging of tumor oxygenation by using a low-field magnetic resonance scanner and a paramagnetic contrast agent is described. The methodology is based on Overhauser enhanced magnetic resonance imaging (OMRI), a functional imaging technique. OMRI experiments were performed on tumor-bearing mice (squamous cell carcinoma) by i.v. administration of the contrast agent Oxo63 (a highly derivatized triarylmethyl radical) at nontoxic doses in the range of 2-7 mmol/kg either as a bolus or as a continuous infusion. Spatially resolved pO 2 (oxygen concentration) images from OMRI experiments of tumor-bearing mice exhibited heterogeneous oxygenation profiles and revealed regions of hypoxia in tumors (<10 mmHg; 1 mmHg ‫؍‬ 133 Pa). Oxygenation of tumors was enhanced on carbogen (95% O 2͞5% CO2) inhalation. The pO2 measurements from OMRI were found to be in agreement with those obtained by independent polarographic measurements using a pO 2 Eppendorf electrode. This work illustrates that anatomically coregistered pO 2 maps of tumors can be readily obtained by combining the good anatomical resolution of water proton-based MRI, and the superior pO 2 sensitivity of EPR. OMRI affords the opportunity to perform noninvasive and repeated pO 2 measurements of the same animal with useful spatial (Ϸ1 mm) and temporal (2 min) resolution, making this method a powerful imaging modality for small animal research to understand tumor physiology and potentially for human applications.A bnormal values of pO 2 (the partial pressure of O 2 ) are linked to many pathophysiological conditions (e.g., ischemic diseases, reperfusion injury, and oxygen toxicity). Approximately one-third of human tumors evaluated for oxygen status have shown significant oxygen deficiency, and oxygen deficiency increases the tumor's resistance toward cancer treatment modalities, including radiation and chemotherapy (1, 2). Additionally, hypoxic microenvironments in tumors are known to promote processes driving malignant progression, such as angiogenesis, elimination of p53 tumor suppressor activity, genetic instability, and metastasis (3-5). Understanding of tumor hypoxia could lead to the discovery of diagnostic and prognostic markers for malignant progression, discovery of novel therapeutic targets, and the development of new constructs for gene therapy applications in human cancer. Hence, a noninvasive technique that could accurately and repetitively measure tissue oxygenation would find broad application in clinical and basic research. Unfortunately, the currently used electrochemical method (6) for in vivo oxygen measurement is an invasive technique applicable only to accessible tumors. Further, the technique is hampered by measurements of only a small part of the total tumor, which cannot be re-evaluated. Several magnetic resonance techniques (7, 8) have been developed for in vivo oximetry, including spin label oximetry (9), MRI (10), and electron paramagnetic resonance imaging (EPRI) (11,12). The blood oxygen level-dependent...

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Small SAAs (≤25 mm) are not prone to significant expansion and do not require frequent surveillance imaging. Imaging every 3 years for small SAAs is adequate. Aneurysms of the pancreaticoduodenal arcade and gastroduodenal aneurysms are more likely to rupture and therefore warrant a more aggressive interventional approach.

The paramagnetic spin probe Oxo63 is used in oximetric imaging studies based on electron paramagnetic resonance (EPR) methods by monitoring the oxygen-dependent linewidth while minimizing the contributions from self-broadening seen at high probe concentrations. Therefore, it is necessary to determine a suitable dose of Oxo63 for EPR-based oxygen mapping where the self-broadening effects are minimized while signal intensity adequate for imaging can be realized. A constant tissue concentration of spin probe would be useful to image a subject and assess changes in pO 2 over time; accumulation or elimination of the compound in specific anatomical regions could translate to and be mistaken for changes in local pO 2 , especially in OMRI-based oximetry. The in vivo pharmacokinetics of the spin probe, Oxo63, after bolus and/or continuous intravenous infusion was investigated in mice using a novel approach with X-band EPR spectroscopy. The results show that the half-life in blood was 17-21 min and the clearance by excretion was 0. A number of techniques currently have the capability to assess tissue oxygen tension or are under development (1,2). Clarke-type oxygen electrodes are widely used experimentally and clinically to estimate pO 2 levels, although only a small portion of the tissue is sampled (3,4). However, results from such measurements over the past several years have shown a strong correlation between tumor pO 2 and treatment outcome, suggesting that tumor oxygenation status is a useful prognostic factor (5). Ideally, a method of oxygen measurement in tissue, e.g., a tumor, should be noninvasive, quantitative, and global with respect to the volume of interest. In addition, such techniques should allow for measurement in tissue before, during, and after treatment. Noninvasive imaging techniques such as blood oxygen level-dependent MRI (BOLD-MRI), single photon emission computed tomography (SPECT), and positron-emission tomography (PET) (6 -9) are now used to assess tumor oxygenation.BOLD-MRI examines differences in T 2 contrast between two images, based on the ratio of diamagnetic oxy-hemoglobin and paramagnetic deoxy-hemoglobin in the blood, and provides qualitative assessment of pO 2 (10,11). PET uses positron-emitting radioisotope-labeled molecular probes such as 18 F-fluoromisonidazole ( 18 F-MISO) (12-14) or 64 Cu-diacetyl-bis(N 4 -methylthiosemicarbazone) ( 64 Cu-ATSM) (15-17), which have high affinity for the hypoxic atmosphere and obtain spatial maps of hypoxic regions in a patient and/or experimental animals. Measurement of oxygen metabolism was clinically carried out by PET using 15 O gas as the probe (18 -22). SPECT is also a radiological imaging technique which has been used for measurement of blood perfusion volume in the brain employing a ␥-ray emitting radioisotope such as N-isopropyl-p- Noninvasive imaging techniques based on electron paramagnetic resonance (EPR) such as continuous wave (CW) and time-domain electron paramagnetic resonance imaging (EPRI) (11,33,34), or Overhauser-enhanced MRI (OMR...