Incorporating Oxygen-Enhanced MRI into Multi-Parametric Assessment of Human Prostate Cancer

Abstract

Hypoxia is associated with prostate tumor aggressiveness, local recurrence, and biochemical failure. Magnetic resonance imaging (MRI) offers insight into tumor pathophysiology and recent reports have related transverse relaxation rate (R2*) and longitudinal relaxation rate (R1) measurements to tumor hypoxia. We have investigated the inclusion of oxygen-enhanced MRI for multi-parametric evaluation of tumor malignancy. Multi-parametric MRI sequences at 3 Tesla were evaluated in 10 patients to investigate hypoxia in prostate cancer prior to radical prostatectomy. Blood oxygen level dependent (BOLD), tissue oxygen level dependent (TOLD), dynamic contrast enhanced (DCE), and diffusion weighted imaging MRI were intercorrelated and compared with the Gleason score. The apparent diffusion coefficient (ADC) was significantly lower in tumor than normal prostate. Baseline R2* (BOLD-contrast) was significantly higher in tumor than normal prostate. Upon the oxygen breathing challenge, R2* decreased significantly in the tumor tissue, suggesting improved vascular oxygenation, however changes in R1 were minimal. R2* of contralateral normal prostate decreased in most cases upon oxygen challenge, although the differences were not significant. Moderate correlation was found between ADC and Gleason score. ADC and R2* were correlated and trends were found between Gleason score and R2*, as well as maximum-intensity-projection and area-under-the-curve calculated from DCE. Tumor ADC and R2* have been associated with tumor hypoxia, and thus the correlations are of particular interest. A multi-parametric approach including oxygen-enhanced MRI is feasible and promises further insights into the pathophysiological information of tumor microenvironment.

Combined MR Imaging of Oxygen Consumption and Supply Reveals Tumor Hypoxia and Aggressiveness in Prostate Cancer Patients

“…Positron emission tomography (PET) with hypoxia-specific tracers has been successful in several cancer types (6), but has failed to detect hypoxia in this disease (7). Magnetic resonance imaging (MRI) approaches like blood oxygenation level-dependent (BOLD) imaging or related techniques to measure oxygenation directly are challenging and far from routine use (8)(9)(10). Moreover, indirect hypoxia measures, including vascular parameters derived from dynamic contrast enhanced (DCE)-MRI (11), have not shown the specificity needed for a hypoxia biomarker in prostate cancer, as demonstrated in preclinical work (12).…”

Imaging tumour hypoxia with oxygen-enhanced MRI and BOLD MRI

“…[56][57][58][59]61 or in patient tumours. 65,99 These generally describe complex and non-linear relationships, possibly reflecting spatial or temporal heterogeneity with subregions of luxurious and inadequate perfusion present simultaneously and sometimes seen (with temporal disconnect) in the same voxel. However, potential confounds exist in both measurements; for example ΔR 1 can be confounded by inflow effects, ΔR 2 * can be confounded by presence of haemorrhage and both parameters can be confounded by oxygen-induced vasoconstriction and by vascular steal (Figure 8).…”

Translating preclinical MRI methods to clinical oncology

“…It should be noted that longitudinal relaxation is very sensitive to changes in temperature, and therefore physiological stability is vital. Motivated by these data, clinical applications of BOLD and TOLD have been reported for a range of human cancers. While oxygen‐sensitive measurements are not included currently in standard‐of‐care, the required pulse sequences are routine, and an oxygen breathing challenge can readily be included in the typical time allotted to a routine radiological examination.…”