Size-dependent ferrohydrodynamic relaxometry of magnetic particle imaging tracers in different environments

Size-dependent ferrohydrodynamic relaxometry of magnetic particle imaging tracers in different environments
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DOI:
10.1118/1.4810962
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发表时间:
2013-07-01
期刊:
影响因子:
3.8
通讯作者:
Krishnan, Kannan M.
Krishnan, Kannan M.
中科院分区:
医学3区
文献类型:
--
作者:
Arami, Hamed;Ferguson, R. M.;Krishnan, Kannan M.

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目的:磁性粒子成像(MPI)是最近开发的成像技术,其寻求提供直接源自超顺磁性氧化铁纳米粒子(NP)的正对比度的高分辨率和示踪剂灵敏度。MPI信号可以从响应于施加的磁场的NP的Neel弛豫、布朗旋转扩散和滞后反转机制的组合产生。当需要特异性靶向器官,如癌细胞和内皮心血管细胞时,由于布朗运动的完全或部分消除,在固定的NP中可以预期不同的行为。在这里,作者提出了MPI空间分辨率和信号强度的实验研究作为一个广泛的范围内的中值核心大小的纳米粒子在四个代表性的条件下,包括固定在组织等效介质。方法:具有中值核直径(d(0))的单分散疏水性NP范围为7 - 22 nm,在有机介质中合成,随后在表面改性后分散在水溶液中。研究了纳米颗粒的形态、中值粒径、粒径分布和磁性。将不同核尺寸的疏水性和亲水性纳米粒子分别固定在三辛基氧化膦和琼脂糖凝胶中。他们的大小依赖性能MPI示踪剂的系统矩阵和x-空间图像重建进行了评估,使用磁粒子光谱法(MPS),并与自由旋转people.Results相比:固定化核直径小于类似20 nm的纳米粒子有类似的空间分辨率,但较低的信号强度时,与他们的自由旋转的同行。与它们在溶液中的性能相比,当核尺寸为22 nm的较大NPs固定在琼脂糖中时,空间分辨率得到提高,但信号强度较低。当考虑系统矩阵或x空间方法时,在信号强度中观察到相同的趋势。当NP浓度降低至15 μ g/ml时,谐波和dm/dH信号强度呈线性变化,空间分辨率不发生变化。结论:结果表明MPI信号对NP大小和环境非常敏感。作者的计算表明,布朗旋转扩散比场切换周期慢,因此,它对MPS信号的影响很小。dm/dH分析表明,Neel弛豫是决定较小NP(d(0)<类似于20 nm)中MPI响应的主要机制。较大的NP显示滞后反转时,施加的磁场振幅是足够大的,以克服的反极性。MPS信号强度随铁浓度的线性变化,但具有均匀的空间分辨率,使得定量成像能够用于一系列应用,从高浓度团注追踪成像到低浓度分子成像(虽然作者的仪器是噪声限制的,类似于毫摩尔铁浓度,但理论上,预计MPI具有纳摩尔灵敏度)。这些结果为作者合成的示踪剂用于固定化或体内靶向组织MPI的未来应用铺平了道路。(C)2013年美国医学物理学家协会。
Purpose: Magnetic particle imaging (MPI) is a recently developed imaging technique that seeks to provide ultrahigh resolution and tracer sensitivity with positive contrast directly originated from superparamagnetic iron oxide nanoparticles (NPs). MPI signals can be generated from a combination of Neel relaxation, Brownian rotational diffusion, and hysteretic reversal mechanisms of NPs in response to applied magnetic fields. When specific targeting of organs, such as carcinoma and endothelial cardiovascular cells, is needed, different behavior may be expected in immobilized NPs, due to complete or partial elimination of the Brownian motion. Here, the authors present an experimental investigation of the MPI spatial resolution and signal intensities as a function of a wide range of median core sizes of NPs under four representative conditions, including after immobilization in a tissue equivalent medium.Methods: Monodisperse hydrophobic NPs with median core diameters (d(0)) ranging from 7 to 22 nm were synthesized in organic media and subsequently dispersed in aqueous solution after a facile surface modification. Morphology, median size, size distribution, and magnetic properties of the NPs were investigated. Hydrophobic and hydrophilic NPs with various core sizes were immobilized in trioctyl phosphine oxide and agarose gel, respectively. Their size-dependent performance as MPI tracers for system matrix and x-space image reconstruction was evaluated using magnetic particle spectrometry (MPS) and compared with the free rotating counterparts.Results: Immobilized NPs with core diameters smaller than similar to 20 nm have similar spatial resolution, but lower signal intensities when compared with their free rotating counterparts. Compared to their performance in solution, spatial resolution was improved, but signal intensity was lower, when larger NPs with core size of 22 nm were immobilized in agarose. Same trends were observed in signal intensities, when considering either system matrix or x-space approaches. The harmonic and dm/dH signal intensities changed linearly and the spatial resolution did not change with decreasing NP concentration up to 15 mu g/ml.Conclusions: The results show that the MPI signal is very sensitive to both NP size and environment. The authors' calculations show that Brownian rotational diffusion is slower than the field switching cycle and, therefore, it has minimal influence on MPS signals. dm/dH analyses show that Neel relaxation is the dominant mechanism determining MPI response in smaller NPs (d(0) < similar to 20 nm). Larger NPs show hysteretic reversal when the applied field amplitude is large enough to overcome the coercivity. Linear variation of the MPS signal intensity with iron concentration but with uniform spatial resolution enables quantitative imaging for a range of applications, from high-concentration bolus chase imaging to low-concentration molecular imaging (while the authors' instrument is noise-limited to similar to millimolar iron concentrations, nanomolar sensitivity is expected for MPI, theoretically). These results pave the way for future application of the authors' synthesized tracers for immobilized or in vivo targeted MPI of tissues. (C) 2013 American Association of Physicists in Medicine.