Nano-Metamaterial: A State-of-the-Art Material for Magnetic Resonance Imaging

Abstract

Metamaterials are artificially designed materials with multilevel-ordered microarchitectures, which exhibit extraordinary properties not occurring in nature, and their applications have been widely exploited in various research fields. However, the progress of metamaterials for biomedical applications is relatively slow, largely due to the limitations in the size tailoring. When reducing the maximum size of metamaterials to nanometer scale, their multilevel-ordered microarchitectures are expected to obtain superior functions beyond conventional nanomaterials with single-level microarchitectures, which will be a prospective candidate for the next-generation diagnostic and/or therapeutic agents. Here, a forward-looking discussion on the superiority of nano-metamaterials for magnetic resonance imaging (MRI) according to the imaging principles, which is attributed to the unique periodic arrangement of internal multilevel structural units in nano-metamaterials, is presented. Moreover, recent advances in the development of nano-metamaterials for high-performance MRI are introduced. Finally, the challenges and future perspectives of nano-metamaterials as promising MRI contrast agents for biomedical applications are briefly commented.

Keywords: contrast agents; magnetic resonance imaging; metamaterials; multilevel microarchitectures.

Figure 1

a) The critical features of nickel alloy layered metamaterials across seven orders of magnitude in length scale. Reproduced with permission.^{[ 2 ]} Copyright 2016, Springer Nature. b) Schematic illustration of a ferroelectric nano‐metamaterial with a 2D Archimedean lattice structure. Reproduced under the terms of the CC‐BY Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0).^{[ 11 ]} Copyright 2015, The Authors, published by Springer Nature.

Figure 2

Schematic illustration of the structure of conventional MRI contrast agents (paramagnetic small‐molecule complexes and magnetic nanoparticles with single‐level microarchitectures) and nano‐metamaterials. Owing to the unique multilevel microarchitectures, nano‐metamaterials hold great potential to enhance the important parameters affecting the relaxation times of water protons and thus carve out a new horizon in the field of MRI.

Figure 3

Schematic illustration of the mechanism for the enhanced T ₂ and T ₁ relaxation of water protons in magnetic nano‐metamaterials. Regarding T ₂ relaxation rates, the dense multilevel periodically arranged microarchitectures of nano‐metamaterials contribute to a significant enhancement of the overall magnetization, and thus affecting the diffusion rate of water protons. Besides, the unique structural features of nano‐metamaterials can promote the interaction of water molecules with the internal paramagnetic ions, and trap water molecules in the interstices of their complicated microarchitectures, which lead to larger q, longer ${\tau }_{\mathrm{m}},\hspace{0.17em}\hspace{0.17em}$and ${\tau }_{\text{R\hspace{0.17em}}}$ than those of conventional nanoparticulate contrast agents, thus accelerating the T ₁ relaxation of water protons.

Figure 4

a) Schematic illustration of the fabrication of Fe³⁺–OCPCs based on the novel dual‐kinetic control strategy. b) Transmission electron microscopy (TEM) image of monodisperse Fe³⁺ _0.06–OCPCs; scale bar: 500 nm. c) High‐resolution TEM image of Fe³⁺ _0.06–OCPCs slices (pseudocolor). d) Scanning electron microscopy (SEM) images of Fe³⁺–OCPCs produced at different Fe³⁺ concentrations of 0, 0.02, 0.04, and 0.06 mm, respectively. Scale bar: 100 nm. e) T ₁ relaxation rate of water proton at the presence of Fe³⁺ _0.06–OCPCs, Fe³⁺ _0.02–OCPCs, and Fe³⁺ _0.06–P2VP. f) Schematic diagram of the relationship between the microarchitectures of Fe³⁺ _0.06–P2VP nano‐metamaterial and MRI performance. g) In vivo T ₁ contrast enhancement of Fe³⁺ _0.06–P2VP, Fe³⁺ _0.02–OCPCs, and Fe³⁺ _0.06–OCPCs in mice with subcutaneous axillary tumors after 30 min intratumor injection. a–g) Reproduced under the terms of the CC‐BY Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0).^{[ 52 ]} Copyright 2023, The Authors, Wiley‐VCH.