A biomarker of cancer aggressiveness, such as hypoxia, could substantially impact treatment decisions in the prostate, especially radiation therapy, by balancing treatment morbidity (urinary incontinence, erectile dysfunction, etc.) against mortality. R2* mapping with Mono-Exponential (ME) decay modeling has shown potential for identifying areas of prostate cancer hypoxia at 1.5T. However, Gaussian deviations from ME decay have been observed in other tissues at 3T. The purpose of this study is to assess whether gradient-echo signal decays are better characterized by a standard ME decay model, or a Gaussian Augmentation of the Mono-Exponential (GAME) decay model, in the prostate at 3T. Multi-gradient-echo signals were acquired on 20 consecutive patients with a clinical suspicion of prostate cancer undergoing MR-guided prostate biopsies. Data were fitted with both ME and GAME models. The information content of these models were compared using Akaike’s Information Criterion (second-order, AICC), in skeletal muscle, the prostate central gland (CG), and peripheral zone (PZ) regions-of-interest (ROIs). The GAME model had higher information content in 30% of the prostate on average (across all patients and ROIs), covering up to 67% of cancerous PZ ROIs, and up to 100% of cancerous CG ROIs (in individual patients). The higher information content of GAME became more prominent in regions that would be assumed hypoxic using ME alone, reaching 50% of the PZ and 70% of the CG as ME R2* approached 40 s−1. R2* mapping may have important applications in MRI; however, information lost due to modeling could mask differences in parameters due to underlying tissue anatomy or physiology. The GAME model improves characterization of signal behavior in the prostate at 3T, and may increase the potential for determining correlates of fit parameters with biomarkers, such as of oxygenation status.

Purpose To assess whether R2* mapping with a standard Mono-Exponential (ME) or a Gaussian Augmentation of the Mono-Exponential (GAME) decay model better characterizes gradient-echo signal decays in gynecological cancers after external beam radiation therapy at 3T, and evaluate implications of modeling for non-invasive identification of intra-tumoral hypoxia. Materials and Methods Multi-gradient-echo signals were acquired on 25 consecutive patients with gynecologic cancers and three healthy participants during inhalation of different oxygen concentrations at 3T. Data were fitted with both ME and GAME models. Models were compared using F-tests in tumors and muscles in patients, muscles, cervix and uterus in healthy participants, and across oxygenation levels. Results GAME significantly improved fitting over ME (P <0.05): Improvements with GAME covered 34% of tumor regions-of-interest on average, ranging from 6% (of a vaginal tumor) to 68% (of a cervical tumor) in individual tumors. Improvements with GAME were more prominent in areas that would be assumed hypoxic based on ME alone, reaching 90% as ME R2* approached 100 Hz. GRE decay parameters at different oxygenation levels were not significantly different (P = 0.81). Conclusion R2* may prove sensitive to hypoxia, however, inaccurate representations of underlying data may limit the success of quantitative assessments. Although the degree to which R2 or σ values correlate with hypoxia remains unknown, improved characterization with GAME increases the potential for determining any correlates of fit parameters with biomarkers, such as oxygenation status.