Blood oxygen level dependent (BOLD) contrast MRI and breast cancer chemotherapy response

Abstract

10514 Background: Tumor microcirculation and oxygenation play critical roles in tumor growth and response to cytotoxic treatment. Assessing these parameters in vivo may provide a useful tool for evaluating therapy in real time. Deoxyhemoglobin (dHbO2) can serve as an endogenous contrast agent causing signal loss in echo planar MR images. Tumor characteristics or interventions affecting tumor oxygenation, which convert dHbO2 to HbO2 produce a BOLD signal gain, may complement conventional MRI. Material and Methods: Ten patients with locally advanced breast cancer received doxorubicin and cyclophosphamide (AC) for four cycles every 2 or 3 weeks followed by paclitaxel for 4 cycles. Prior to chemotherapy and after 1 and 4 cycles of AC, MRI was performed on a 1.5 T scanner. For the BOLD study, patients breathed room air (RA) for 45 sec, then oxygen for 6 min and finally RA again. The BOLD imaging an Echo Planar technique with TR/TE (500/41.4 ms) 256 matrix and 20cm field of view. This was followed by dynamic contrast enhanced (DCE) MRI study. Pre and 1 to 4 day post-treatment tumor biopsies for hypoxia response proteins by immunohistochemistry and global RNA by gene array expression analysis (Illumina platform) were obtained. Results: MRI showed mild BOLD contrast enhancing regions in all evaluable patients with a typical signal enhancement of ∼2%. All 3 patients with an initial high BOLD-effect (>7%) achieved a pathological response after chemotherapy compared to 4 who did not (p < 0.03). The MRI-DCE tumor response signal decreased with chemotherapy, but no correlation with pathological response was seen. No clear difference in hypoxia-induced proteins (eg. HIF1-alpha, VEGF, CAIX) was seen according to pathological response or BOLD. Distinct gene expression patterns at baseline and after therapy emerged depending on BOLD response involving development, apoptosis and cell cycle pathways. Discussion: BOLD MRI can provide a non-invasive, easily repeatable in vivo approach to assess breast tumor physiology and its sensitivity to hypoxia (vascular oxygenation) may add value by measuring hypoxia and predicting response to therapy. BOLD MRI appears promising to select ideal candidates for hypoxia targeting with anti-angiogenic agents combined with chemotherapy and such studies are under way. No significant financial relationships to disclose.