Ultrasound methods for quantitative imaging of the distribution of magnetic nanoparticles in biological tissue in connection with drug delivery concepts and magnetic hyperthermia for localized tumor treatment

纳米粒子在医学诊断和治疗中具有极大的兴趣。由于单个纳米颗粒的小尺寸，可以使用所谓的EPR效应（增强的渗透性和保留），其允许在它们经由血管施用后，从血管强渗透到生物组织中并对组织产生强烈影响。这尤其适用于肿瘤组织，因为其血管孔通常会扩大。磁性纳米颗粒可以通过磁场移动，空间聚集和加热，这使得它们对肿瘤治疗很感兴趣。计划中的项目涉及两种方法：（a）局部化疗，其中使用电磁体从体外将携带药物的磁性纳米颗粒局部积聚在肿瘤组织中，并以这种方式将药物释放到肿瘤组织区域。这种减少常规化疗副作用的方法被称为磁性药物靶向（MDT）。在第二种方法（B）磁热疗（MH）中，使用交变磁场加热颗粒并热作用于组织。尽管磁共振成像（MRI）和磁粒子成像（MPI）原则上适用于此，但这些模态复杂且难以应用于MDT和MH治疗方法中。相比之下，众所周知超声波是一种不太复杂且易于使用的方式。然而，由于它们的小尺寸，纳米颗粒在超声中仅产生极弱的反向散射，并且在常规超声图像中不可见。在“磁动”方法中，纳米颗粒被交变磁场刺激，进行周期性运动，并传递到周围的生物组织中，从而使颗粒运动间接可见，并通过超声和颗粒分布定性显示。逆概念也允许颗粒密度的定量测定。第二种方法利用了被纳米颗粒穿透的组织改变了整体机械性质的事实，弹性性能因此，可以使用超声弹性成像来可视化和量化颗粒密度。基于我们自己的初步工作的令人鼓舞的结果，这些程序将被进一步开发和研究，作为所描述的治疗程序的一部分。同时，通过修改纳米颗粒合成来检查影响颗粒的代表性和可量化性的机会。研究应首先在体模上进行，然后在动物实验中进行。

Nanoparticles are of great interest in medical diagnostics and therapy. Because of the small size of single nanoparticles, the so-called EPR effect (Enhanced Permeability and Retention) can be used which allows, after their administration via blood vessels, a strong penetration from the vessels into biological tissue and an intensive impact on the tissue. This applies in particular to tumor tissue since its vascular pores are often enlarged.Magnetic nanoparticles can be moved, spatially accumulated and heated by magnetic fields, which makes them interesting for tumor therapy. The planned project involves two methods: (a) localized chemotherapy, in which drug-carrying magnetic nanoparticles are locally accumulated in the tumor tissue from outside the body using an electromagnet and can in this way release the drugs in the tumor tissue area. This procedure, which reduces the side effects of conventional chemotherapy, is known as Magnetic Drug Targeting (MDT). In the second method, (b) Magnetic Hyperthermia (MH), the particles are heated using an alternating magnetic field and act thermally on the tissue.In both cases, there is a need to monitor the spatial distribution of the particles in the tissue areas to be treated and to quantitatively determine the particle density. Although Magnetic Resonance Imaging (MRI) and Magnetic Particle Imaging (MPI) are suitable in principle for this, these modalities are complex and difficult to apply in the MDT and MH therapy methods. In contrast, ultrasound is known to be a less complex and easy-to-use modality. However, due to their small sizes, nanoparticles only generate extremely weak backscatter in ultrasound and are not visible in conventional ultrasound images. Therefore, special effects have to be utilized for a sonographic detection and visualization of the nanoparticles.In the "magneto-motive" approach, the nanoparticles are stimulated by alternating magnetic fields to perform periodic movements that are transferred to the surrounding biological tissue, making the particle movements indirectly visible with ultrasound and particle distributions qualitatively displayed. An inverse concept also allows a quantitative determination of the particle density. A second approach takes advantage of the fact that the tissue penetrated by nanoparticles changes the bulk mechanical, e.g., elastic properties. The particle density can thus be visualized and quantified using ultrasound elastography. Based on the encouraging results of our own preliminary work, these procedures are to be further developed and investigated as part of the therapy procedures described. At the same time, the chance is examined to influence the representation and quantifiability of the particles by modifying the nanoparticle synthesis. The investigations shall initially be carried out on phantoms and later in animal experiments.