Reeves D, Brown S, Fiering S, Weaver J
Dartmouth College, Hanover, NH.
Dartmouth-Hitchcock Medical Center, Lebanon, NH.
Med Phys. 2012 Jun;39(6Part5):3643. doi: 10.1118/1.4734798.
Magnetic spectroscopy of Brownian motion (MSB) has been used previously to measure temperature, viscosity, and cellular binding in vitro. The MSB signal - a ratio of the 5th to 3rd harmonic of the response from magnetic nanoparticles to an oscillating field - provides insight into particle microenvironment. These biosensing capabilities would be productive in vivo but until now were prevented by sensitivity limits. Our goal was to design and create a similar apparatus for work in vivo. In vivo spectroscopy is a viable precursor to imaging, and is essential for drug delivery or therapeutic methods like hyperthermia.
Coil geometries were modeled to optimize a uniform Helmholtz drive coil and imaging coil with maximal spatial resolution. The completed apparatus includes balancing and trim coils to zero out unwanted background fields. The coils were characterized and experiments were performed to verify consistency with previous in vitro experiments. Finally, as an in vivo experiment, we took MSB spectra on living mice with five week old melanomas injected with 200ug of 100nm starch coated nanoparticles.
The drive coil is capable of sustaining 12.5mT fields up to 1.5kHz with a field variation of 3% throughout the sample volume. The pickup coil is frequency independent and has a vertical and horizontal range of 5mm and 10mm respectively before the MSB signal drops below 50%. The minimum sensitivity is 50-70μg of iron. MSB signal response to viscosity changes shows the same signatures as the in vitro apparatus. The in vivo data showed successful sensing of nanoparticles. We also saw the MSB signal decay with time showing the apparatus can detect changes in particle behavior due to interactions with biology.
We achieved in vivo MSB and due to sufficient sensitivity we are motivated to further work in monitoring in vivo cellular uptake and viscosity.
布朗运动磁谱（MSB）此前已用于体外测量温度、粘度和细胞结合。MSB信号——磁性纳米颗粒对振荡场响应的五阶谐波与三阶谐波之比——可深入了解颗粒微环境。这些生物传感能力在体内应用会很有成效，但迄今为止，灵敏度限制阻碍了其发展。我们的目标是设计并制造一种类似的用于体内工作的仪器。体内光谱学是成像的可行前身，对于药物递送或热疗等治疗方法至关重要。
对线圈几何结构进行建模，以优化具有最大空间分辨率的均匀亥姆霍兹驱动线圈和成像线圈。完整的仪器包括平衡线圈和微调线圈，以消除不需要的背景场。对线圈进行了表征，并进行了实验以验证与先前体外实验的一致性。最后，作为一项体内实验，我们对患有五周龄黑色素瘤且注射了200μg 100nm淀粉包被纳米颗粒的活体小鼠进行了MSB光谱测量。
驱动线圈能够在高达1.5kHz的频率下维持12.5mT的磁场，在整个样品体积内磁场变化为3%。拾取线圈与频率无关，在MSB信号降至50%以下之前，其垂直和水平范围分别为5mm和10mm。最小灵敏度为50 - 70μg铁。MSB信号对粘度变化的响应显示出与体外仪器相同的特征。体内数据表明成功检测到了纳米颗粒。我们还观察到MSB信号随时间衰减，表明该仪器能够检测由于与生物相互作用导致的颗粒行为变化。
我们实现了体内MSB，由于具有足够的灵敏度，我们有动力进一步开展监测体内细胞摄取和粘度的工作。
