BackgroundFor intraoperative imaging in operating theaters or preoperative imaging in clinics, compact and economic integration rather than large and expensive equipment is required to coregister structural and functional imaging. However, current technologies, such as those integrating optical and gamma cameras or infrared and fluorescence imaging, involve certain drawbacks, including the radioactive biorisks of nuclear medicine indicators and the inconvenience of conducting measurements in dark environments.MethodsTo specifically and magnetically label liver tumors, an anti-alpha-fetoprotein (AFP) reagent was synthesized from biosafe iron oxide magnetic nanoparticles (MNPs) coated with anti-AFP antibody and solved in a phosphate buffered saline solution. In addition, a novel dual-imaging model system integrating an optical camera and magnetic scanning superconducting-quantum-interference device (SQUID) biosusceptometry (SSB) was proposed. The simultaneous coregistration of low-field magnetic images of MNP distributions and optical images of anatomical regions enabled the tumor distribution to be determined easily and in real time. To simulate targeted MNPs within animals, fewer reagents than the injected dose were contained in a microtube as a sample for the phantom test. The phantom test was conducted to examine the system characteristics and the analysis method of dual images. Furthermore, the animal tests were classified into two types, with liver tumors implanted either on the backs or livers of rats. The tumors on the backs were to visually confirm the imaging results of the phantom test, and the tumors on the livers were to simulate real cases in hepatocellular carcinoma people.ResultsA phantom test was conducted using the proposed analysis method; favorable contour agreement was shown between the MNP distribution in optical and magnetic images. Consequently, the positioning and discrimination of liver tumors implanted on the backs and livers of rats were verified by conducting in vivo and ex vivo tests. The results of tissue staining verified the feasibility of using this method to determine the distribution of liver tumors.ConclusionThe results of this study indicate the clinical potential of using anti-AFP-mediated MNPs and the dual-imaging model SSB for discriminating and locating tumors.

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 alpha-fetoprotein antibody (anti-AFP) MNP distribution on gauzes. In animal tests, rats with liver tumors were imaged at the pre-injection 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.