New Imaging Methods for Functional Changes in Diagnostic Nanocomposite Particles

背景：无机/有机纳米复合颗粒（I/O-NP）正在被开发用于诊断医学。I/O-NP是一种平台技术，它由功能聚合物有机纳米结构（50-200纳米）组成，其中封装了较小的金属纳米颗粒（2-20纳米）。通过微调纳米结构组成和结构，I/O-NPs提供了一类新的生物响应功能材料。磁性氧化铁纳米颗粒在生物反应性有机纳米结构中的封装正在开发中；聚合物颗粒被设计成在生物刺激下膨胀或收缩，导致颗粒间接近度和被封装的氧化铁纳米颗粒旋转动力学的可逆变化，这将引发其磁信号的响应行为。这种刺激可以通过量身定制的I/O-NP合成来实现，以纳入疾病特异性靶向载体或抗体，从而在响应药物干预时对疾病病原体和病毒载量进行量化。在个体病人的基础上，这种定量的疾病状态监测将加速从传统医学向个性化、精准医学的过渡。从长期来看，从对药物剂量反应的更大患者队列监测中获得的数据将被整合到计算机模型中，以便对医疗处方有更大的预测能力，允许以人口为导向的预测建模，以优化全球药物方案的管理。问题：生物刺激后I/O-NP结构离散的关键功能变化的检测。I/O-NPs提供了传统诊断成像示踪剂之外的新功能。然而，目前的标准检测方法无法监测其关键功能变化；MRI等成像技术以及SQUID等实验室技术的灵敏度不足以检测到磁信号的这种细微变化。解决方案：开发一个原型扫描仪，称为FS-MPI。该装置将磁化率的频率相关检测原理与磁粉成像的超灵敏检测机制相结合。MPI是一种高灵敏度的新兴成像技术，能够检测纳米摩尔浓度的超顺磁性氧化铁纳米颗粒（SPION）示踪剂。磁示踪剂成像直接允许高灵敏度，定量检测无背景信号。此外，MPI允许定量和实时功能成像，在每摩尔的基础上，MPI比MRI的噪声对比度提高了1000倍以上，提供了明亮的对比度。通过将MPI与铁磁和超顺磁薄膜纳米结构表征技术（例如交流磁化率；解决方案提供商的背景）相结合，提出了一种新的FS-MPI成像模式，为检测此类变化提供了前景。MPI技术是由示踪剂开发驱动的，因此，如果与探测这些功能示踪剂的新成像模式相结合，则通过先进材料研究代表了巨大的新颖性和创新潜力。用于测量I/O-NP功能行为的原型FS-MPI系统的开发是非常雄心勃勃的，新型I/O-NP材料开发和用于检测的原型成像设备的结合将为体内和体外的新诊断技术创造巨大的创新潜力。

Background: Inorganic/Organic Nanocomposite Particles (I/O-NP) are being developed for use in diagnostic medicine. I/O-NP is a platform technology that is composed of functional polymeric organic nanoscale structures (50-200 nm) in which smaller metallic nanoparticles (2-20 nm) are encapsulated. I/O-NPs offer a new class of biologically responsive, functional materials through fine tuning nanostructure composition and architecture. The encapsulation of magnetic iron oxide nanoparticles within biologically responsive organic nanostructures are being developed; polymeric particles are designed to swell or contract in response to biological stimuli, causing reversible variation of interparticle proximity and rotation dynamics of the encapsulated iron oxide nanoparticles, which would elicit a responsive behaviour in their magnetic signal. Such stimuli could be achieved through tailored I/O-NP synthesis to incorporate disease specific targeting vectors or antibodies, allowing for disease pathogen and viral load quantification in response to pharmaceutical intervention. On an individual patient basis, such quantitative disease state monitoring would accelerate the transition from conventional medicine towards personalised, precision medicine. In the long-term, acquired data from larger patient cohort monitoring following response to drug dosage would be integrated into in-silico models to allow for greater predictive power for medical prescription, allowing for population driven predictive modelling towards optimising global drug regimen administration.Problem: The detection of discrete, key functional changes in I/O-NP structure following biological stimulation. I/O-NPs offer novel functionality beyond traditional diagnostic imaging tracers. However, current standard detection methods are not capable of monitoring their key functional changes; imaging techniques such as MRI as well as laboratory techniques such as SQUID are not sensitive enough to detect such fine variation of magnetic signal.Solution: To develop a prototype scanner, termed FS-MPI. The proposed novel device combines the principles of frequency dependent detection of magnetic susceptibility (FS) with the ultrasensitive detection mechanism of Magnetic Particle Imaging (MPI). MPI is a highly sensitive, emerging imaging technique able to detect nanomolar concentrations of Superparamagnetic Iron Oxide Nanoparticle (SPION) tracers. Magnetic tracers are imaged directly allowing for highly sensitive, quantitative detection with no background signal. Furthermore, MPI allows for both quantification and real-time functional imaging with more than a thousand-fold contrast-to-noise improvement on a per-mole basis over MRI, providing bright contrast. Through the combination of MPI with techniques established for characterising ferromagnetic and superparamagnetic thin film nanostructures (e.g. AC susceptibility; the background of the Solution Provider), a new FS-MPI imaging modality is proposed which offers the prospect of detecting such changes. MPI technologies are driven by tracer development and thus represents enormous potential for novelty and innovation through Advanced Materials Research if coupled with new imaging modalities for probing such functional tracers. Development of a prototype FS-MPI system designed to measure the functional behaviour of I/O-NP is highly ambitious, and the combination of novel I/O-NP material development and prototype imaging device for detection will create enormous potential for innovation for new diagnostic technologies, both in vivo and in vitro.