The effect of flow on blood oxygen level dependent (R*2 ) MRI of orthotopic lung tumors

Abstract

Purpose: Blood oxygen level dependent (BOLD) MRI based on ${\text{R}}_2^{*}$ measurements can provide insights into tumor vascular oxygenation. However, measurements are susceptible to blood flow, which may vary accompanying a hyperoxic gas challenge. We investigated flow sensitivity by comparing ${\text{R}}_2^{*}$ measurements with and without flow suppression (fs) in 2 orthotopic lung xenograft tumor models.

Methods: H460 (n = 20) and A549 (n = 20) human lung tumor xenografts were induced by surgical implantation of cancer cells in the right lung of nude rats. MRI was performed at 4.7T after tumors reached 5 to 8 mm in diameter. A multiecho gradient echo MRI sequence was acquired with and without spatial saturation bands on each side of the imaging plane to evaluate the effect of flow on ${\text{R}}_2^{*}$ . fs and non-fs ${\text{R}}_2^{*}$ MRI measurements were interleaved during an oxygen breathing challenge (from air to 100% O₂ ). ${\text{T}}_2^{*}$ -weighted signal intensity changes (ΔSI(%)) and ${\text{R}}_2^{*}$ measurements were obtained for regions of interest and on a voxel-by-voxel basis and discrepancies quantified with Bland-Altman analysis.

Results: Flow suppression affected ΔSI(%) and ${\text{R}}_2^{*}$ measurements in each tumor model. Average discrepancy and limits of agreement from Bland-Altman analyses revealed greater flow-related bias in A549 than H460.

Conclusion: The effect of flow on ${\text{R}}_2^{*}$ , and hence BOLD, was tumor model dependent with measurements being more sensitive in well-perfused A549 tumors.

Keywords: blood oxygen level dependent (BOLD); flow-suppression; hypoxia; lung cancer; oxygen-sensitive MRI.