Colloidal Nanoparticles for MRI Contrast Agents
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 T1 imaging and high feasibility on detection of lesion of T2 imaging.1

Method

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

1. Zhou Z, Huang D, Bao J, Chen Q, Liu G, Chen Z, Chen X and Gao J, et al. A synergistically enhanced T1–T2 dual-modal contrast agent. Adv. Mater. 2012, 24: 6223–6228.

2. Jung H, Park B, Lee C, Cho J, Suh J, Park J, Kim Y, Kim J, Cho G, Cho H et al. Dual MRI T1 and T2(*) contrast with size-controlled iron oxide nanoparticles. Nanomed Nanotech, Bio Med. 2014;10 (8):1679 – 1689.

3. Sharma V, Alipour 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.

4. Lee N, Choi Y, Lee Y, Park M, K. Moon WK, Choi SH, Hyeon T, et al. Water-dispersible ferrimagnetic iron oxide nanocubes with extremely high r2 relaxivity for highly sensitive in vivo MRI of tumors. Nano Lett. 2012, 12: 3127–3131.

Figures

Fig 1. a) TEM image of 9.7 nm nanocubes distributed in Hexane. b) M-H curve of iron oxide nanocubes.

Fig 2. Simultaneous enhancement of T1 and T2 contrast effect. a) T1-and T2- weighted images of SPIO nanocubes at different concentration in water. b.c) r1 and r2 relaxivity analysis vs, SPIO nanocubes concentration at room temperature.

Fig 3. Dual-mode imaging of kidney on a 3T MRI scanner. a) T1-weighted and b) T2-weighted in vivo MR images of Sprague Dawley rat on transverse plane before and after IV injection.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
2832