In-Vivo Imaging of Cell Migration Using Contrast Enhanced MRI and SVM Based Post-Processing.

Christian Weis,Andreas Hess,Lubos Budinsky,Ben Fabry

doi:10.1371/journal.pone.0140548

Abstract

The migration of cells within a living organism can be observed with magnetic resonance imaging (MRI) in combination with iron oxide nanoparticles as an intracellular contrast agent. This method, however, suffers from low sensitivity and specificty. Here, we developed a quantitative non-invasive in-vivo cell localization method using contrast enhanced multiparametric MRI and support vector machines (SVM) based post-processing. Imaging phantoms consisting of agarose with compartments containing different concentrations of cancer cells labeled with iron oxide nanoparticles were used to train and evaluate the SVM for cell localization. From the magnitude and phase data acquired with a series of -weighted gradient-echo scans at different echo-times, we extracted features that are characteristic for the presence of superparamagnetic nanoparticles, in particular hyper- and hypointensities, relaxation rates, short-range phase perturbations, and perturbation dynamics. High detection quality was achieved by SVM analysis of the multiparametric feature-space. The in-vivo applicability was validated in animal studies. The SVM detected the presence of iron oxide nanoparticles in the imaging phantoms with high specificity and sensitivity with a detection limit of 30 labeled cells per mm3, corresponding to 19 μM of iron oxide. As proof-of-concept, we applied the method to follow the migration of labeled cancer cells injected in rats. The combination of iron oxide labeled cells, multiparametric MRI and a SVM based post processing provides high spatial resolution, specificity, and sensitivity, and is therefore suitable for non-invasive in-vivo cell detection and cell migration studies over prolonged time periods.

Highlights

Histological studies of cell migration in animal models require sacrificing the animals
Features characteristic for the presence of iron oxide particles were extracted from magnitude (Fig 2) and phase data (Fig 3)
Applying the support vector machines (SVM)-model on these features gives a 3D map in which each voxel is classified as either containing iron oxide and not containing iron oxide (Fig 4A)

Summary

Introduction

Histological studies of cell migration in animal models require sacrificing the animals. The data obtained from any given animal is limited to a single point in time. For certain processes such as the formation of metastases, regional tumor growth and micrometastatic. In-Vivo Imaging of Cell Migration Using MRI and SVM progression, the colonization of biomaterials with cells, or the migration of stem cells, it is essential to observe the distribution pattern of injected cells in the same animal at multiple time points. Limitations of OI-based cell tracking techniques include limited depth of penetration, limited quantification and poor spatial resolution due to photon scatter [2]. CT, and MRI allow for tracking of cell position at any tissue depth at the expense of some detail, sensitivity, and specificity [3]

Methods

Results

Conclusion