Magnetic nanoparticles for MR imaging: agents, techniques and cardiovascular applications

Abstract

Magnetic nanoparticles (MNP) are playing an increasingly important role in cardiovascular molecular imaging. These agents are superparamagnetic and consist of a central core of iron-oxide surrounded by a carbohydrate or polymer coat. The size, physical properties and pharmacokinetics of MNP make them highly suited to cellular and molecular imaging of atherosclerotic plaque and myocardial injury. MNP have a sensitivity in the nanomolar range and can be detected with T1, T2, T2*, off resonance and steady state free precession sequences. Targeted imaging with MNP is being actively explored and can be achieved through either surface modification or through the attachment of an affinity ligand to the nanoparticle. First generation MNP are already in clinical use and second generation agents, with longer blood half lives, are likely to be approved for routine clinical use in the near future.

Fig. 1

Schematic representation of advances in magnetic nanoparticle (MNP) design. MNP agents currently under development will have significantly higher relaxivities than earlier generations of MNP, and will also have improved synthetic coats for targeted imaging

Fig. 2

Panel a: conventional T2* weighted gradient echo imaging (echo time 6.5 ms) in three mice injected with CLIO-Cy5.5 48 h after infarction [31]. The injected doses were (I) 3 mg Fe/kg, (II) 10 mg Fe/kg and (III) 20 mg Fe/kg. Accumulation of the probe in macrophages produced signal hypointensity (negative contrast) in the injured anterolateral wall (arrows). A clear and fairly linear dose response was seen, even at doses significantly higher than those that could be given clinically. Panel b: conventional T2* weighted gradient echo imaging in a single mouse injected with 20 mg Fe/kg of CLIO-Cy5.5 48 h after infarction [31]. The images shown were obtained with an echo time of (I) 2.7 ms, (II) 3.5 ms and (III) 6.5 ms. The thinned infarcted anterolateral wall is clearly seen at the shortest echo time and develops negative contrast, due to MNP accumulation, only once the echo time is increased

Fig. 3

Imaging of cardiomyocyte apoptosis by MRI at 9.4 Tesla in mice in vivo [33]. The mice were injected with the annexin labeled MNP, AnxCLIO-Cy5.5, after transient coronary ligation. Accumulation of the probe was seen in the hypokinetic anterior wall of all mice injected with AnxCLIO-Cy5.5, as shown above (arrows). However, no accumulation of the unlabeled control probe, CLIO-Cy5.5, was seen in any of the mice

Fig. 4

Dual modality imaging of the magnetofluorescent contrast agent, CLIO-Cy5.5 [31]. (see also Fig. 2 above). The images shown are: a coronal MR image of the thorax, through the plane of the heart, used for co-alignment with fluorescence tomography images of the heart and thorax. b 2D coronal slice at the level of the heart from a 3D fluorescence tomographic dataset. The fluorescence image has been overlaid onto a white light image of the mouse. The depth resolved 3D fluorescence dataset has been acquired completely non-invasively with a dedicated small animal fluorescence tomography system. Significant fluorescence signal is seen over the heart of an infarcted mouse, further confirming the presence of the MNP in the myocardium. c No significant fluorescence intensity is seen over the heart of a sham operated mouse