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Updated: Jun 23, 2026

A Label-free Technique for the Spatio-temporal Imaging of Single Cell Secretions
Published on: November 23, 2015
Self-refocused spatial-spectral pulse for positive contrast imaging of cells labeled with SPIO nanoparticles
Priti Balchandani1, Mayumi Yamada, John Pauly
1Department of Radiology, Stanford University, Stanford, California 94305-5488, USA. pritib@stanford.edu
Abstract:
MRI has been used extensively to noninvasively track the location of cells labeled with superparamagnetic iron-oxide nanoparticles (SPIOs) in vivo. Typically, SPIOs are employed as a negative contrast agent which makes it difficult to differentiate labeled cells from extraneous sources of inhomogeneity and actual voids in the image. As a result, several novel approaches have been put forth to obtain positive contrast from SPIOs. One technique proposed by Cunningham et al. utilizes spectrally selective pulses to excite and refocus spins in the vicinity of the SPIOs. Although the frequency selectivity of this technique provides effective positive contrast, the lack of slice selectivity results in interfering signal from sources of off-resonance outside the slice of interest. We have developed a self-refocused spatial-spectral (SR-SPSP) pulse to achieve slice-selective spin-echo imaging of off-resonant spins. Using a self-refocused pulse affords flexibility in echo-time selection since the spin echo may be placed at any time after the end of the pulse. The spatial selectivity achieved by the SR-SPSP RF pulse eliminates background signal from out-of-slice regions and reduces the on-resonant water suppression requirements. Phantom and in vivo data demonstrate that positive contrast and slice-selectivity are achieved using this novel RF pulse.
Insights
This study introduces a novel self-refocused spatial-spectral pulse for MRI. This technique enhances positive contrast imaging of superparamagnetic iron-oxide nanoparticle-labeled cells while improving slice selectivity.
Area of Science:
- Magnetic Resonance Imaging (MRI)
- Biomedical Engineering
- Nanotechnology
Background:
- Superparamagnetic iron-oxide nanoparticles (SPIOs) are used for cell tracking in MRI.
- SPIOs typically act as negative contrast agents, complicating cell detection.
- Existing positive contrast methods lack slice selectivity, leading to image artifacts.
Purpose of the Study:
- To develop a novel radiofrequency (RF) pulse for slice-selective spin-echo imaging.
- To achieve positive contrast imaging of off-resonant spins near SPIOs.
- To overcome limitations of existing SPIO contrast enhancement techniques.
Main Methods:
- Development of a self-refocused spatial-spectral (SR-SPSP) pulse.
- Implementation of slice-selective spin-echo imaging.
- Phantom and in vivo experiments to validate the pulse performance.
Main Results:
- The SR-SPSP pulse successfully achieved slice-selective imaging.
- Positive contrast was obtained from SPIO-labeled cells.
- Background signals from out-of-slice regions were eliminated.
- Reduced requirements for on-resonant water suppression.
Conclusions:
- The novel SR-SPSP pulse enables accurate, slice-selective positive contrast MRI of SPIO-labeled cells.
- This technique improves the differentiation of labeled cells from image artifacts.
- The method offers flexibility in echo-time selection for optimized imaging.

