Detection threshold of single SPIO-labelled cells with FIESTA

University of Toronto, Toronto, Ontario, Canada
Magnetic Resonance in Medicine (Impact Factor: 3.57). 02/2005; 53(2):312-20. DOI: 10.1002/mrm.20356
Source: PubMed


MRI of superparamagnetic iron oxide (SPIO)-labeled cells has become a valuable tool for studying the in vivo trafficking of transplanted cells. Cellular detection with MRI is generally considered to be orders of magnitude less sensitive than other techniques, such as positron emission tomography (PET), single photon emission-computed tomography (SPECT), or optical fluorescence microscopy. However, an analytic description of the detection threshold for single SPIO-labeled cells and the parameters that govern detection has not been adequately provided. In the present work, the detection threshold for single SPIO-labeled cells and the effect of resolution and SNR were studied for a balanced steady-state free precession (SSFP) sequence (3D-FIESTA). Based on the results from both theoretical and experimental analyses, an expression that predicts the minimum detectable mass of SPIO (m(c)) required to detect a single cell against a uniform signal background was derived: m(c) = 5v/(K(fsl) x SNR), where v is the voxel volume, SNR is the image signal-to-noise ratio, and K(fsl) is an empirical constant measured to be 6.2 +/- 0.5 x 10(-5) microl/pgFe. Using this expression, it was shown that the sensitivity of MRI is not very different from that of PET, requiring femtomole quantities of SPIO iron for detection under typical micro-imaging conditions (100 microm isotropic resolution, SNR = 60). The results of this work will aid in the design of cellular imaging experiments by defining the lower limit of SPIO labeling required for single cell detection at any given resolution and SNR.

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Available from: Chris V Bowen, Apr 15, 2014
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    • "lung, bones) or in the presence of haemorrhages (because of the paramagnetism of de-oxy haemoglobin). Furthermore, the IONP-labelled cells generated contrast is linearly correlated to the cells number only at low iron concentrations [6] [7]. *Address correspondence to this author at the Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy, Via Nizza 52, 10126 – Torino, Italy; Tel: +39-0116706452; Fax: +39-0116706487; E-mail: "

    Full-text · Article · Jul 2015
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    • "In addition, iron-labeled cell quantification is difficult. We, and others, have shown that the contrast generated by iron-labeled cells increases with the amount of iron/voxel but that this is only linear at low iron loadings; the change in contrast reaches a saturation plateau at higher iron loadings.6,7 When quantifying the presence of iron-labeled stem cells over time, most studies measure the “signal void volume”8,9 or the “number of black pixels”,10,11 and present the change relative to the first imaging time point. "
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    ABSTRACT: Mesenchymal stem cells (MSC) are used to restore deteriorated cell environments. There is a need to specifically track these cells following transplantation in order to evaluate different methods of implantation, to follow their migration within the body, and to quantify their accumulation at the target. Cellular magnetic resonance imaging (MRI) using fluorine-based nanoemulsions is a great means to detect these transplanted cells in vivo because of the high specificity for fluorine detection and the capability for precise quantification. This technique, however, has low sensitivity, necessitating improvement in MR sequences. To counteract this issue, the balanced steady-state free precession (bSSFP) imaging sequence can be of great interest due to the high signal-to-noise ratio (SNR). Furthermore, it can be applied to obtain 3D images within short acquisition times. In this paper, bSSFP provided accurate quantification of samples of the perfluorocarbon Cell Sense-labeled cells in vitro. Cell Sense was internalized by human MSC (hMSC) without adverse alterations in cell viability or differentiation into adipocytes/osteocytes. The bSSFP sequence was applied in vivo to track and quantify the signals from both Cell Sense-labeled and iron-labeled hMSC after intramuscular implantation. The fluorine signal was observed to decrease faster and more significantly than the volume of iron-associated voids, which points to the advantage of quantifying the fluorine signal and the complexity of quantifying signal loss due to iron.
    Full-text · Article · Apr 2014 · International Journal of Nanomedicine
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    • "Obviously MRI does not reach microscopic resolution; (Heyn et al., 2005; Martin, 2011), for in vivo experiments, the detection limit is in the range between 100 and 500 cells (Heyn et al., 2005; Muja and Bulte, 2009). This is relevant insofar, as final diagnosis is based on the cellular (type and shape) and molecular information (surface epitopes expressed by the cells) derived from histology. "
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