Akbar Alipour1,2,3, Vijay Kumar Shamra3,4, Zeliha Soran Erdem3, Zaliha Gamze Aykut5, and Hilmi Volkan Demir2,3,4
1UMRAM-National Magnetic Resonance Research Center, Bilkent University, Ankara, Turkey, 2Department of Electrical and Electronics Engineering, Bilkent University, Ankara, Turkey, 3UNAM – Institute of Materials Science and Nanotechnology, Bilkent University, Ankara, Turkey, 4School of Mathematical and Physical Sciences, Nanyang Technological University, Singapore, Singapore, 5Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey
Synopsis
Magnetic resonance imaging (MRI) contrast agents, employed as
image contrast enhancement mechanism, are able to change either negative or
positive signal intensity. T2 contrast normally offers magnetic
susceptibility artifacts and decreases the resolution. On the other hand, T1 contrast
provides high spatial resolution, but it suffers from the deficiency of high
contrast-to-noise ratio, which limits their clinical applications. To overcome
the aforementioned limitations, we offer cubic shape super-paramagnetic iron
oxide nanoparticles (SPIONs) as dual-mode colloidal MRI contrast agents. The in
vitro and in vivo T1 and T2 MR images promise
the great potential clinical application of SPIO nanocubes as dual-mode MR
contrast agent.Purpose
The purpose of this study is to synthesize highly crystalline
SPIONs as dual-mode colloidal MRI contrast agent to provide accurate diagnosis
information by combining both the high tissue resolution of T
1 imaging
and high feasibility on detection of lesion of T
2 imaging.
1Method
Among different clinical
applications of magnetic nanoparticles, contrast enhancing magnetic resonance
mechanism is one of the major implementations of these nanoparticles. MRI
sensitivity can be significantly enhanced by using contrast agent, typically in
the form of T1 and
T2 contrast agents. T1
imaging, normally using paramagnetic particles as
the contrast materials, increase MR signal intensity
consequently lead to high resolution between tissues. However it has high
contrast-to-noise ratio. SPIONs have been most widely used as dominant T2 MRI
contrast agent because of their strong magnetization and bio-compatibility.
However, the main problem of the SPIO nanoparticles in MRI is the magnetic
susceptibility artifacts which cause dark MR images.2 Although
SPIONs are T2-weighted materials, Zhou et al. reported that very
small iron oxide nanoparticles, approximately 3 nm in diameter, can provide T1-
weighted (positive contrast) effect in MRI.1 In
our presented study, we
suggested a dual- modal contrast agent for MRI.3 The unique
advantages of combing T1 and
T2 imaging possibility into a single form of contrast
agent is very useful for clinical applications. Accurate and entire diagnostic
knowledge can be achieved by integration of various image modalities in both T1-weighted
imaging with excellent tissue resolution and T2-weighted imaging
with better possibility on lesion identification.4 We
synthesized highly crystalline SPIO nanoparticles in cubic shape using thermal
decomposition technique. The transmission microscopy (TEM) image indicates that
monodisperse cubic shaped nanoparticles are achieved with a size of ~ 9.7 nm
(Fig 1a). The field- dependent magnetization curve (M-H) shows that
cubic-shape nanoparticles behave in both super- paramagnetic and paramagnetic
regime simultaneously (Fig 1b).
To investigate the dual-mode MR contrast enhancement effect of
silica coated SPIO nanocubes, we obtained multiecho spinecho sequence T1 and T2-weighted images at different SPION
concentrations. The following sequence parameters were considered: TR = 1000,
TE = 12 ms (For T1), TR = 10000, TE = 330 ms (For T2), Flip angle = 90°, Flice
thickness = 3 mm, FoV = 120 × 120 mm2,
Acquisition matrix = 384 pixels × 384 pixels.
By increasing the SPION concentration we observed increased signals in T1-weighted
MR images and decreased signals in T2-weighted MR images (Fig 2a).
The MRI relaxivity (r1, r2) values of cubic nanoparticles
were calculated using equation (1) and the results are shown in Figure
2b,c. $$$
r_{1,2}=R_{pre1,2}-R_{post1,2} $$$. Which
Rpre1,2 and Rpost1,2
are the relaxation rates before and after contrast agent, respectively.
We then demonstrated the T1 and
T2 dual-mode in vivo MR imaging of SPIO nanocubes with a
3T MRI scanner. Using a Sprague Dawley (200-250 g) rat as a model, we obtained
T1 and T2-weighted images before and after IV
injection of SPION, with the dose of 1mg kg-1. We focused on the
kidney as interested region. The results demonstrated that T1-weighted
MR image represents a brighter signal, and obviously darker signal was achieved
in T2-weighted MR image at transverse plane, 1 hour after injection
(Fig 3a, b). The investigation of MR signal variation in the kidney as a region
of interest noticed that the signal intensity significantly changes on both T1 and
T2 imaging. These results indicated that SPIO nanocubes
show dual-mode MR contrast enhancement, which can provide more exhaustive
clinical information and consequently more accurate diagnosis.
In this study, we reported a dual-mode MR contrast agent which can
be implemented in kidney imaging. The in vivo T1 and T2 MR
images promise the great potential clinical application of SPIO nanocubes as
dual-mode MR contrast agent.
Acknowledgements
The authors gratefully thank support from
Scientific and Technological Research Council of Turkey, TUBITAK 109E002, 109E004. We also gratefully acknowledge UMRAM staff for providing technical support. References
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Bao J, Chen Q, Liu G, Chen Z, Chen X and Gao J, et al. A synergistically enhanced T1–T2 dual-modal
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J, Park J, Kim
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G, Cho H et al. Dual MRI T1 and T2(*)
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A, Erdem Z, Aykut G, Demir H, et al. Highly monodisperse low-magnetization magnetite
nanocubes as simultaneous T1–T2 MRI contrast agents. Nanoscale, 2015, 7: 10519–10526.
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T, et al. Water-dispersible ferrimagnetic iron oxide nanocubes with extremely
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