Ultrasound-Induced Magnetic Imaging of Tumors Targeted by Biofunctional Magnetic Nanoparticles Kai-Wen Huang,†,‡ Jen-Jie Chieh,*,§ Chih-Kuang Yeh,∥ Shu-Hsien Liao,§ Yi-Yan Lee,§ Pei-Yi Hsiao,§ Wen-Chun Wei,§ Hong-Chang Yang,§ and Herng-Er Horng§ †
Department of Surgery and Hepatitis Research Center, National Taiwan University Hospital, 100 Taipei, Taiwan Graduate Institute of Clinical Medicine, National Taiwan University, 100 Taipei, Taiwan § Institute of Electro-Optical Science and Technology, National Taiwan Normal University, 116 Taipei, Taiwan ∥ Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, 300 Hsinchu, Taiwan ‡
S Supporting Information *
ABSTRACT: Biofunctional magnetic nanoparticles (MNPs) have been widely applied in biomedical engineering. MNPs are used as a contrast medium in magnetic imaging. Current methods of magnetic imaging, such as magnetic particle imaging and magnetic relaxometry, use small amounts of MNPs at target points far from the surface of the patient’s body; these methods always consume considerable power to produce magnetic fields of high uniformity or gradient excitations. Some drawbacks, such as a limited imaging region, imaging system shielding, and complex algorithms based on assumptions of MNP properties or environmental factors, also limit the application of MNP methods in clinics. Therefore, this work proposes an interdisciplinary methodology of ultrasound-induced magnetic imaging that lacks these drawbacks. In the proposed imaging method, magnet sets were designed with uniform magnetic fields to magnetize MNPs. Besides, magnetized MNPs are subjected to ultrasound vibrations; the motion of the MNPs induces weak induction voltages at the imaging pickup coils. The highly sensitive scanning superconducting quantum interference device biosusceptometry with three sets of ultrasound focus chips was developed to construct magnetic tomography at three depths. A phantom test showed favorable consistency between the visual photos and the magnetic images of alphafetoprotein antibody (anti-AFP) MNP distribution on gauzes. In animal tests, rats with liver tumors were imaged at the preinjection and post-injection of anti-AFP MNPs. The consistent results of magnetic images and ultrasound images implied that the proposed method has high clinical potential. KEYWORDS: magnetic nanoparticles, ultrasound-induced magnetic imaging, superconducting quantum interference device, tumors, alpha-fetoprotein
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anoparticles have been extensively used for in vivo biomedical applications, such as imaging contrast media1 and drug carriers.2,3 An increasing number of disciplines such as theranostics are developing multifunctional nanoparticles for drug delivery and contrast agents.4 Magnetic nanoparticles (MNPs) offer crucial advantages, such as biosafety,5,6 molecular imaging,7 distribution manipulation,8 hyperthermia,9 and drug treatment, that cannot be delivered by radioactive, optical, and ultrasound nanoparticles. Thus, MNPs have been frequently used in clinics as commercial reagents for in vivo imaging (Ferucarbotran, Resovist, Germany) or examination (Sienna+, Endomagnetics, UK; MF-CEA-0061, MagQu, Taiwan). MNP imaging technologies are under development because the superior magnetic characteristics of MNPs satisfy key clinical requirements, such as low cost and © XXXX American Chemical Society
easy operation for high-population clinics, compatible mechanisms of functional imaging with structural imaging for complete medical imaging, adequate spatial resolution for early discrimination of tumors, and sufficient time resolution for tracking drug delivery. For example, a study showed that high-field magnetic resonance imaging (MRI) performed well because the uniformity of the magnetic field was destroyed by MNPs, and the T2-imaging brightness darkened in the targeted region.1 However, there were still some deficiencies, such as limited Received: December 30, 2016 Accepted: February 27, 2017
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DOI: 10.1021/acsnano.6b08730 ACS Nano XXXX, XXX, XXX−XXX
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magnetometer have a common mechanism, namely, the vibration of a sample to generate a detectable magnetic signal. The difference is that a vibration sample magnetometer utilizes a mechanical vibration motor and a linking holder to shake a sample at some low frequency, typically
