Abstract
Histopathological level imaging in a non-invasive manner is important for clinical diagnosis, which has been a tremendous challenge for current imaging modalities. Recent development of ultra-high-field (UHF) magnetic resonance imaging (MRI) represents a large step toward this goal. Nevertheless, there is a lack of proper contrast agents that can provide superior imaging sensitivity at UHF for disease detection, because conventional contrast agents generally induce T2 decaying effects that are too strong and thus limit the imaging performance. Herein, by rationally engineering the size, spin alignment, and magnetic moment of the nanoparticles, we develop an UHF MRI-tailored ultra-sensitive antiferromagnetic nanoparticle probe (AFNP), which possesses exceptionally small magnetisation to minimize T2 decaying effect. Under the applied magnetic field of 9 T with mice dedicated hardware, the nanoprobe exhibits the ultralow r2/r1 value (~1.93), enabling the sensitive detection of microscopic primary tumours (<0.60 mm) and micrometastases (down to 0.20 mm) in mice. The sensitivity and accuracy of AFNP-enhanced UHF MRI are comparable to those of the histopathological examination, enabling the development of non-invasive visualization of previously undetectable biological entities critical to medical diagnosis and therapy.
Highlights
Histopathological level imaging in a non-invasive manner is important for clinical diagnosis, which has been a tremendous challenge for current imaging modalities
X-ray diffraction (XRD) patterns reveal that different-sized antiferromagnetic nanoparticle probe (AFNP) have identical FePt3 (JCPDS no. 29-0716) crystalline structures (Supplementary Fig. 1)
The Fe/Pt molar ratios of AFNPs are determined to be ~1:3 by inductively coupled plasmamass spectrometry (ICP-MS) (Supplementary Table 1)
Summary
Histopathological level imaging in a non-invasive manner is important for clinical diagnosis, which has been a tremendous challenge for current imaging modalities. By rationally engineering the size, spin alignment, and magnetic moment of the nanoparticles, we develop an UHF MRI-tailored ultra-sensitive antiferromagnetic nanoparticle probe (AFNP), which possesses exceptionally small magnetisation to minimize T2 decaying effect. The sensitivity and accuracy of AFNP-enhanced UHF MRI are comparable to those of the histopathological examination, enabling the development of non-invasive visualization of previously undetectable biological entities critical to medical diagnosis and therapy. Once conjugated with the cyclic arginyl–glycyl–aspartic acid (RGD) peptide (cRGDyK) for neovasculature targeting, these antiferromagnetic nanoprobes enable UHF MRI to detect primary small tumours and micrometastases with high sensitivity and accuracy, providing detailed information about the microscopic tumours as small as 0.20 mm, which to date could only be revealed by histopathological examination. We anticipate the antiferromagnetic nanoprobes as demonstrated are ideal candidates for the future development of UHF-competent high-performance contrast agents, to maximise the utility of the next-generation UHF MRI for the visualisation of previously undetectable biological lesions
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