Precision magnetic hyperthermia by integrating magnetic particle imaging

集成磁粉成像的精密磁热疗法 磁性氧化铁纳米颗粒(MIONPs)的磁活化为许多人提供了巨大的潜力 生物医学应用。批准的临床应用包括磁共振的对比增强 磁共振成像(MRI)和磁流体热疗(MFH)用于癌症治疗。MIONPs为T2负对比度 自20世纪80年代末以来临床上可用于核磁共振的药物，其组织浓度非常低 (&lt；100g Fe/g组织)进行成像。MFH是一种基于纳米技术的强大疗法，它可以增强 放射治疗(RT)。它包括通过用外部交替物激活MIONPs来局部加热组织 磁场(AMF)，可以在身体的任何地方进行治疗。人体临床试验证明了 MFH治疗前列腺癌；放疗对复发的胶质母细胞瘤(GBM)患者的总体生存好处 2010年，欧洲批准了这一计划。然而，当前MFH的有效性受到无法可视化MIONP的限制 在MFH期间的分布，导致AMF对MIONP加热的不良控制，降低了治疗效果，以及 不想要的偏离目标的毒性。一种集成的MIONP成像-MFH技术，提供空间控制 MFH的治疗量将大大促进医用MIONPs的临床应用。磁粉 成像(MPI)是一种新兴的成像技术，它可以直接定量组织中的MIONP浓度 与核磁共振的敏感性相似或更高。MPI扫描仪中的主磁铁产生强磁场 包含磁场近似为零的区域的梯度，即无场区域(FFR)。 FFR中的MIONPs是磁性不饱和的，可以在接收器线圈中产生信号，而MIONPs 其他地方是磁饱和的，不会产生任何信号。图像是通过对FFR进行栅格扫描来生成的 样本。用于成像的FFR可用于MFH的定位。通过施加磁场梯度和 AMF，只有FFR内的MIONP会发热，而FFR外的MIONPs是饱和的，不会发热。MPI 和MFH兼容，可实现MFH的毫米精度空间控制。我们的目标是开发一种综合的 MPI/MFH工作流程，将影像引导的治疗计划与最佳的MIONPs治疗相结合 小动物(小鼠和大鼠)模型的临床前生物医学研究。我们的目标是通过以下方式实现目标 购买Hyper AMF系统，该系统将与我们最近收购的Momentum MPI扫描仪一起使用(资助 由S10共享仪器拨款)。我们的具体目标是：(目标1)确定具有理想体格的MIONPs 和MPI/MFH的磁性；(目标2)开发MPI引导的MFH治疗方法 建模和调幅；(目标3)显示治疗鼻窦炎的疗效增加 MPI/MFH体内移植。虽然拟议工作的主要目标是技术开发，但成功 这些目标的完成将为生物医学研究人员提供实现治疗鼻音应用的能力 磁性纳米颗粒。

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.