Quantitative evaluation of optimal imaging parameters for single-cell detection in MRI using simulation ☆ Ali-Reza Mohammadi-Nejad a , Gholam-Ali Hossein-Zadeh a,b , Hamid Soltanian-Zadeh a,b,c, ⁎ a Control and Intelligent Processing Center of Excellence, School of Electrical and Computer Engineering, University of Tehran, Tehran, Iran b Signal and Image Processing Group, School of Cognitive Sciences, Institute for Studies in Theoretical Physics and Mathematics (IPM), Tehran, Iran c Department of Radiology, Medical Image Analysis Laboratory, Henry Ford Hospital, Detroit, MI, USA Received 14 December 2007; revised 20 August 2009; accepted 25 November 2009 Abstract Super-paramagnetic iron oxide (SPIO) nanoparticles are actively investigated to enhance disease detection through molecular imaging using magnetic resonance imaging (MRI). Detection of the cells labeled by SPIO depends on the MRI protocols and pulse sequence parameters that can be optimized. To evaluate the sensitivity and specificity of the image acquisition methods and to obtain optimal imaging parameters for single-cell detection, we further developed an MRI simulator. The simulator models an object (tissue) at a microscopic level to evaluate effects of spatial distribution and concentration of nanoparticles on the resulting image. In this study, the simulator was used to evaluate and compare imaging of the labeled cells by the gradient-echo (GE), true-FISP [fast imaging employing steady-state acquisition (FIESTA)] and echo-planar imaging (EPI) pulse sequences. Effects of the imaging and object parameters, such as field strength, imaging protocol and pulse sequence parameters, imaging resolution, cell iron load, position of SPIO within the voxel and cell division within the voxel, were investigated in the work. The results suggest that true-FISP has the highest sensitivity for single-cell detection by MRI. © 2010 Elsevier Inc. All rights reserved. Keywords: Molecular imaging; Magnetic resonance imaging (MRI); Simulator; Super-paramagnetic iron-oxide (SPIO) nanoparticles; Optimal pulse sequence parameters; Single-cell detection 1. Introduction Magnetic resonance imaging (MRI) is the method of choice for noninvasive tracking of labeled cells, thanks to its high spatial resolution and the availability of safe contrast agents. Cellular MRI using magnetically labeled cells is now used to study a variety of cellular events. Macrophages and stem cells are of particular interest for diagnosis and therapy of a variety of diseases. To evaluate the effectiveness of the stem cell therapy, it is important to monitor the migration and mobility of the cells. One potential strategy for visualizing cell populations in vivo is to first load them with MRI contrast agents, such as super-paramagnetic iron-oxide (SPIO) nanoparticles [1]. The high susceptibility difference between the particles and the surrounding tissue generates local inhomogeneity of the static magnetic field. This in turn attenuates the MRI signal of the water molecules near the cells and induces signal loss in the T2*-weighted images [2]. Since only a tiny fraction of the injected cells reach their target sites, recent studies have moved towards detecting a small number of cells or even single cells. MRI of single labeled cells opens up a new window into the cell biology by utilizing noninvasive imaging methods for in vivo studies. Over the past few years, there has been a growing interest in refining the MRI hardware (magnetic field strength, detection coils, imaging pulse sequences) and cell labeling methods that allow for the noninvasive tracking of single labeled cells, not only in vitro [3] but also in vivo [4,5]. The benefit of using high-resolution MRI for cellular imaging has been demonstrated by Dodd et al. [6] and recently by Smirnov et al. [7] in an in vitro study. These experiments Available online at www.sciencedirect.com Magnetic Resonance Imaging 28 (2010) 408 – 417 ☆ This work was supported in part by a grant from the University of Tehran, Tehran, Iran. ⁎ Corresponding author. Medical Image Analysis Laboratory, Depart- ment of Radiology, Henry Ford Hospital, Detroit, MI 48202, USA. Tel.: +1 313 874 4482; fax: +1 313 874 4494. E-mail address: hamids@rad.hfh.edu (H. Soltanian-Zadeh). 0730–725X/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.mri.2009.11.001