Bowen Chris V, Zhang Xiaowei, Saab George, Gareau Paula J, Rutt Brian K
Department of Medical Biophysics, University of Western Ontario, London, Ontario, Canada.
Magn Reson Med. 2002 Jul;48(1):52-61. doi: 10.1002/mrm.10192.
The relaxation rates of iron-oxide nanoparticles compartmentalized within cells were studied and found to satisfy predictions of the static dephasing (SD) regime theory. THP-1 cells in cell culture were loaded using two different iron-oxide nanoparticles (superparamagnetic iron-oxide (SPIO) and ultrasmall SPIO (USPIO)) with four different iron concentrations (0.05, 0.1, 0.2, and 0.3 mg/ml) and for five different incubation times (6, 12, 24, 36, and 48 hr). Cellular iron-oxide uptake was assessed using a newly developed imaging version of MR susceptometry, and was found to be linear with both dose and incubation time. R(2)* sensitivity to iron-oxide loaded cells was found to be 70 times greater than for R(2), and 3100 times greater than for R(1). This differs greatly from uniformly distributed nanoparticles and is consistent with a cellular bulk magnetic susceptibility (BMS) relaxation mechanism. The cellular magnetic moment was large enough that R(2)' relaxivity agreed closely with SD regime theory predictions for all cell samples tested [R(2)'=2 pi/(9 x the square root of 3) x gamma LMD] where the local magnetic dose (LMD) is the sample magnetization due to the presence of iron-oxide particles). Uniform suspensions of SPIO and USPIO produced R(2)' relaxivities that were a factor of 3 and 8 less, respectively, than SD regime theory predictions. These results are consistent with theoretical estimates of the required mass of iron per compartment needed to guarantee SD-regime-dominant relaxivity. For cellular samples, R(2) was shown to be dependent on both the concentration and distribution of iron-oxide particles, while R(2)' was sensitive to iron-oxide concentration alone. This work is an important first step in quantifying cellular iron content and ultimately mapping the density of a targeted cell population.
研究了细胞内分隔的氧化铁纳米颗粒的弛豫率,发现其符合静态去相位(SD)机制理论的预测。使用两种不同的氧化铁纳米颗粒(超顺磁性氧化铁(SPIO)和超小SPIO(USPIO)),以四种不同的铁浓度(0.05、0.1、0.2和0.3 mg/ml),并在五种不同的孵育时间(6、12、24、36和48小时)对细胞培养中的THP-1细胞进行加载。使用新开发的磁共振磁化率成像版本评估细胞对氧化铁的摄取,发现其与剂量和孵育时间均呈线性关系。发现R(2)*对负载氧化铁的细胞的敏感性比对R(2)高70倍,比对R(1)高3100倍。这与均匀分布的纳米颗粒有很大不同,并且与细胞体磁化率(BMS)弛豫机制一致。细胞磁矩足够大,以至于对于所有测试的细胞样品,R(2)'弛豫率与SD机制理论预测值非常接近[R(2)' = 2π/(9×√3)×γLMD],其中局部磁剂量(LMD)是由于存在氧化铁颗粒而产生的样品磁化强度)。SPIO和USPIO的均匀悬浮液产生的R(2)'弛豫率分别比SD机制理论预测值低3倍和8倍。这些结果与保证SD机制主导弛豫率所需的每个隔室铁的理论估计质量一致。对于细胞样品,R(2)显示出既取决于氧化铁颗粒的浓度又取决于其分布,而R(2)'仅对氧化铁浓度敏感。这项工作是量化细胞铁含量并最终绘制目标细胞群体密度图的重要第一步。