Detection of iron oxide nanoparticle (IONP)-labeled stem cells using quantitative ultrashort echo time imaging: a feasibility study

BACKGROUND: In this study, we investigated the feasibility of quantitative ultrashort echo time (qUTE) magnetic resonance (MR) imaging techniques in the detection and quantification of iron oxide nanoparticle (IONP)-labeled stem cells. METHODS: A stem cell phantom containing multiple layers of unlabeled or labeled stem cells with different densities was prepared. The phantom was imaged with quantitative UTE (qUTE) MR techniques [i.e., UTE-T(1) mapping, UTE-T(2)* mapping, and UTE-based quantitative susceptibility mapping (UTE-QSM)] as well as with a clinical T(2) mapping sequence on a 3T clinical MR system. For T(1) mapping, a variable flip angle (VFA) method based on actual flip angle imaging (AFI) technique was utilized. For T(2)* mapping and UTE-QSM, multiple images with variable, interleaved echo times including UTE images and gradient recalled echo (GRE) images were used. For UTE-QSM, the phase information from the multi-echo images was utilized and processed using a QSM framework based on the morphology-enabled dipole inversion (MEDI) algorithm. The qUTE techniques were also evaluated in an ex vivo experiment with a mouse injected with IONP-labeled stem cells. RESULTS: In the phantom experiment, the parameters estimated with qUTE techniques showed high linearity with respect to the density of IONP-labeled stem cells (R(2)>0.99), while the clinical T(2) parameter showed impaired linearity (R(2)=0.87). In the ex vivo mouse experiment, UTE-T(2)* mapping and UTE-QSM showed feasibility in the detection of injected stem cells with high contrast, whereas UTE-T(1) and UTE-T(2)* showed limited detection. Overall, UTE-QSM demonstrated the best contrast of all, with other methods being subjected more to a confounding factor due to different magnetic susceptibilities of various types of neighboring tissues, which creates inhomogeneous contrast that behaves similar to IONP. CONCLUSIONS: In this study, we evaluated the feasibility of a series of qUTE imaging techniques as well as conventional T(2) mapping for the detection of IONP-labeled stem cells in vitro and ex vivo. UTE-QSM performed superior amongst other qUTE techniques as well as conventional T(2) mapping in detecting stem cells with high contrast.