Abstract

ObjectivesThis study aimed to evaluate the detectability of stem cells labeled with very small iron oxide particles (VSOP) at 3T with susceptibility weighted (SWI) and T2* weighted imaging as a methodological basis for subsequent examinations in a large animal stroke model (sheep).Materials and MethodsWe examined ovine mesenchymal stem cells labeled with VSOP in agarose layer phantoms. The experiments were performed in 2 different groups, with quantities of 0–100,000 labeled cells per layer. 15 different SWI- and T2*-weighted sequences and 3 RF coils were used. All measurements were carried out on a clinical 3T MRI. Images of Group A were analyzed by four radiologists blinded for the number of cells, and rated for detectability according to a four-step scale. Images of Group B were subject to a ROI-based analysis of signal intensities. Signal deviations of more than the 0.95 confidence interval in cell containing layers as compared to the mean of the signal intensity of non cell bearing layers were considered significant.ResultsGroup A: 500 or more labeled cells were judged as confidently visible when examined with a SWI-sequence with 0.15 mm slice thickness. Group B: 500 or more labeled cells showed a significant signal reduction in SWI sequences with a slice thickness of 0.25 mm. Slice thickness and cell number per layer had a significant influence on the amount of detected signal reduction.Conclusion500 VSOP labeled stem cells could be detected with SWI imaging at 3 Tesla using an experimental design suitable for large animal models.

Highlights

  • Ischemic stroke is one of the primary causes of acquired disability in adults in the western world [1]

  • 500 very small iron oxide particles (VSOP) labeled stem cells could be detected with susceptibility weighted (SWI) imaging at 3 Tesla using an experimental design suitable for large animal models

  • In group A the inter-rater reliability of the four raters was fair to good (Cohen’s Kappa 0.4–0.7) [32]. 100,000 labeled mesenchymal stem cells (MSC) could be detected in all sequences (BRV = 1). 10,000 MSC could be detected with SWI sequences using the 8 channel coil at 0.6 mm and 0.15 mm slice thickness, and with the 12 channel coil deploying a T2* weighted sequence at 0.7 mm slice thickness

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Summary

Introduction

Ischemic stroke is one of the primary causes of acquired disability in adults in the western world [1]. The exact pathophysiological mechanisms and the optimal form of stem cell therapy still need to be elucidated [5,7,8,9] It is still not clear whether a particular stem cell population is required to be present in the brain to unleash optimal therapeutic effect. This is most likely the case for some promising stem cell populations tracking of intracerebrally located cells require larger bores of the MRI scanners, different coils and use lower field strengths in most cases. This results in limitations of the achievable spatial resolution and of the detectability of labeled cells with T2* weighted imaging [20,21]

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