Diffusion Enhanced Sensitivity of bSSFP Quantification of Micron-Sized Superparamgnetic Iron Oxide

Introduction MRI cellular trafficking using superparamagnetic iron oxide (SPIO) is an area of intense research with broad applications in regenerative medicine and immunology research, however a practical quantitative approach that is both sensitive and specific to SPIO has yet to be presented. Quantification in cellular imaging studies is vital to investigate comparative efficacies for regenerative medicine and immunomodulatory therapies. Conventional spin echo (SE) sequences provide SPIO quantification that is very SPIO-cell specific because of inherent refocusing of background magnetic field inhomogeneities (imperfect shim), however SE sensitivity to SPIO labeled cells is unfortunately as much as 70 times less sensitive than gradient echo (GE) techniques [1]. Conversely, GE sequences offer optimal SPIO sensitivity, but artifacts created by field inhomogeneities greatly reduce GE’s SPIO specificity. Most recently, balanced steady state free precession (bSSFP) has demonstrated potential to be the best approach to cellular density imaging, having both SPIO sensitivity comparable to GE acquisitions [2], and preserved specificity from SE-like refocusing of background field inhomogeneities [3]. The potential for SPIO labeled cell quantification using bSSFP was demonstrated, in principle, using a phantom model of SPIO loaded cells and analytic expressions for transverse relaxation rate enhancement [2]. A linear dependence between the transverse relaxation rate enhancement measured using bSSFP (ΔR2 ) and the local magnetic dose (LMD) was demonstrated for Gd-DTPA doped gel containing polystyrene microspheres [2]. To date, no bSSFP sequence practical for quantitative SPIO cellular density imaging applications has been evaluated, and no assessment using SPIO contrast agents has been reported. In this work, we have studied two candidate bSSFP sequences for quantification of ΔR2 . The first, segmented inversion recovery (IR) bSSFP has been proposed for quantifying T1, T2 and Mo by Schmitt et al. [4], and we have adapted the technique for SPIO quantification (ΔR2 ). A second approach, using variable echo time bSSFP acquisitions (VT), was also analyzed for SPIO quantification (ΔR2 ). We show that ΔR2 estimates from both sequences, ΔR2 (IR) and ΔR2 , demonstrate 2-3 times greater sensitivity than ΔR2 from CPMG acquisitions, and with excellent linearity to varied concentration of micron sized particles of iron-oxide (MPIO). The mechanism of this sensitivity enhancement is shown to be from diffusion effects in the MPIO samples.