Taeho Kim ^†‡§, Eric Momin^∥, Jonghoon Choi ^†‡, Kristy Yuan^∥, Hasan Zaidi^∥, Jaeyun Kim ^†‡§, Mihyun Park ^§, Nohyun Lee ^§, Michael T. McMahon ^†⊥, Alfredo Quinones-Hinojosa^∥ , Jeff W. M. Bulte ^†‡¶#, Taeghwan Hyeon ^*§, and Assaf A. Gilad ^{*†‡ ⊥}

^† Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States
^‡ Cellular Imaging Section, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States
^§ National Creative Research Initiative Center for Oxide Nanocrystalline Materials, World Class University program of Chemical Convergence for Energy and Environment, and School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, Korea
^∥ Department of Neurological Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States
^⊥ F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland 21205, United States
^¶ Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States
^# Department of Chemical and Biomolecular Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States

^*Corresponding author : Taeghwan Hyeon, Assaf A. Gilad

Abstract
Mesoporous silica-coated hollow manganese oxide HMnO@mSiO₂ nanoparticles were developed as a novel T₁ magnetic resonance imaging (MRI) contrast agent. We hypothesized that the mesoporous structure of the nanoparticle shell enables optimal access of water molecules to the magnetic core, and consequently, an effective longitudinal (R₁) relaxation enhancement of water protons, which value was measured to be 0.99 (mM^-1s-^-1) at 11.7 T. Adipose-derived mesenchymal stem cells (MSCs) were efficiently labeled using electroporation, with much shorter T₁ values as compared to direct incubation without electroporation, which was also evidenced by signal enhancement on T₁-weighted MR images in vitro. Intracranial grafting of HMnO@mSiO₂-labeled MSCs enabled serial MR monitoring of cell transplants over 14 days. These novel nanoparticles may extend the arsenal of currently available nanoparticle MR contrast agents by providing positive contrast on T₁-weighted images at high magnetic field strengths.