Positive contrast of SPIO-labeled cells by off-resonant reconstruction of 3D radial half-echo bSSFP

This article describes a new acquisition and reconstruction concept for positive contrast imaging of cells labeled with superparamagnetic iron oxides (SPIOs). Overcoming the limitations of a negative contrast representation as gained with gradient echo and fully balanced steady state (bSSFP), the proposed method delivers a spatially localized contrast with high cellular sensitivity not accomplished by other positive contrast methods. Employing a 3D radial bSSFP pulse sequence with half‐echo sampling, positive cellular contrast is gained by adding artificial global frequency offsets to each half‐echo before image reconstruction. The new contrast regime is highlighted with numerical intravoxel simulations including the point‐spread function for 3D half‐echo acquisitions. Furthermore, the new method is validated on the basis of in vitro cell phantom measurements on a clinical MRI platform, where the measured contrast‐to‐noise ratio (CNR) of the new approach exceeds even the negative contrast of bSSFP. Finally, an in vivo proof of principle study based on a mouse model with a clear depiction of labeled cells within a subcutaneous cell islet containing a cell density as low as 7 cells/mm3 is presented. The resultant isotropic images show robustness to motion and a high CNR, in addition to an enhanced specificity due to the positive contrast of SPIO‐labeled cells. Copyright © 2014 John Wiley & Sons, Ltd. We propose a new cell tracking technique based on 3D radial bSSFP half‐echo imaging. Signal recovery of voxels containing paramagnetic loaded cells is achieved by multiple reconstructions of the raw data modulated with an artificial global frequency offset ∆B0add. Background suppression with positive cellular contrast is gained by subtraction of the on‐resonant from modulated data. The proposed method is able to remarkably exceed the cellular CNR values known from negative contrast bSSFP, improving the detection limits for labeled cells.