Precision magnetic hyperthermia by integrating magnetic particle imaging

结合磁粒子成像的精确磁热疗 磁性氧化铁纳米颗粒（MIONP）的磁性活化为许多领域提供了相当大的潜力。 生物医学应用批准的临床应用包括磁共振的对比度增强 磁共振成像（MRI）和磁流体热疗（MFH）用于癌症治疗。MIONP是T2阴性造影剂 自20世纪80年代后期以来临床上可用于MRI的药物， （<100 μ g Fe/g组织）。MFH是一种强大的基于纳米技术的治疗方法， 放射治疗（RT）。它包括通过激活MIONP与外部交替加热来局部加热组织。 磁场（AMF），使治疗在身体的任何地方。人类临床试验证明了 MFH治疗前列腺癌; RT治疗复发性胶质母细胞瘤（GBM）的总生存期获益， 2010年获得欧洲批准。然而，目前的MFH有效性受到无法可视化MIONP的限制 MFH期间的分布，导致MIONP加热的AMF控制不良，治疗效果降低，以及 有害的脱靶毒性。一种集成的MIONP成像-MFH技术，可提供 MFH治疗量将大大推进治疗诊断MIONP的临床使用。磁粉 MPI成像是一种新兴的成像技术，其直接定量组织中的MIONP浓度， 与MRI相似或更高的灵敏度。MPI扫描仪中的主磁体产生强磁场 梯度包含磁场近似为零的区域，即无场区域（FFR）。 FFR中的MIONP是磁不饱和的，并且可以在接收器线圈中产生信号，而MIONP 在其它地方是磁饱和的，不产生信号。通过光栅化血流储备分数生成图像， 示例.用于成像的FFR可用于定位MFH。通过施加磁场梯度， AMF，只有FFR内的MIONP会发热，而FFR外的MIONP饱和，不会发热。MPI 和MFH是兼容的，使得能够实现MFH的毫米精度空间控制。我们的目标是发展一个综合的 MPI/MFH工作流程，将成像引导治疗计划与最佳治疗诊断MIONP相结合， 小动物（小鼠和大鼠）模型的临床前生物医学研究。我们的目标是通过 购买HYPER AMF系统，该系统将与我们最近收购的Momentum MPI扫描仪（已资助 S10共享工具授权）。我们的具体目标是：（目标1）识别具有理想物理特性的MIONP MPI/MFH的磁性能;（目的2）使用计算的MPI引导的MFH治疗 （目的3）证明治疗诊断学的治疗效果增加 体内MPI/MFH。虽然拟议努力的主要目标是技术开发，但成功的 目标的完成将使生物医学研究人员能够实现治疗诊断应用， 磁性纳米粒子

Precision magnetic hyperthermia by integrating magnetic particle imaging Magnetic activation of magnetic iron oxide nanoparticles (MIONPs) offers considerable potential for numerous biomedical applications. Approved clinical applications include contrast enhancement for magnetic resonance imaging (MRI) and magnetic fluid hyperthermia (MFH) for cancer treatment. MIONPs are T2 negative contrast agents which have been clinically available for MRI since the late 1980s where very low tissue concentrations (<100 g Fe/g tissue) are needed for imaging. MFH is a powerful nanotechnology-based treatment that enhances radiation therapy (RT). It comprises local heating of tissue by activating MIONPs with an external alternating magnetic field (AMF), enabling treatment anywhere in the body. Human clinical trials demonstrated benefits of MFH for prostate cancer; and, overall survival benefits with RT in recurrent glioblastoma (GBM) resulted in European approval in 2010. However, current MFH effectiveness is limited by the inability to visualize MIONP distribution during MFH, resulting in poor AMF control of MIONP heating, reduced therapeutic efficacy, and unwanted off-target toxicity. An integrated MIONP imaging-MFH technology that provides spatial control of the MFH treatment volume will substantially advance the clinical use of theranostic MIONPs. Magnetic particle imaging (MPI) is an emerging imaging technology that directly quantitates MIONP concentration in tissue with similar or greater sensitivity as MRI. The main magnet in an MPI scanner produces a strong magnetic field gradient containing a region where the magnetic field is approximately zero, i.e. the Field Free Region (FFR). MIONPs in the FFR are magnetically unsaturated and can produce a signal in a receiver coil, while MIONPs elsewhere are magnetically saturated and produce no signal. Images are produced by rastering the FFR across the sample. The FFR used for imaging can be used to localize MFH. By applying a magnetic field gradient and AMF, only MIONPs inside the FFR will heat while MIONPs outside the FFR are saturated and do not heat. MPI and MFH are compatible enabling mm-precision spatial control of MFH. Our objective is to develop an integrated MPI/MFH workflow that incorporates imaging-guided treatment planning with optimal theranostic MIONPs for preclinical biomedical research with small animal (mouse and rat) models. We aim to achieve our objectives by purchasing a HYPER AMF system that will be used with our recently acquired Momentum MPI scanner (funded by a S10 shared instrumentation grant). Our specific aims are: (Aim 1) Identify MIONPs having ideal physical and magnetic properties for MPI/MFH; (Aim 2) Develop MPI-guided MFH treatment using computational modeling and amplitude modulation; (Aim 3) Demonstrate increased therapeutic efficacy of theranostic MPI/MFH in vivo. While the primary objective of the proposed effort is technology development, successful completion of the aims will provide biomedical researchers the ability to realize theranostic applications with magnetic nanoparticles.