Institute for Biodiagnostics (Atlantic), National Research Council, 1796 Summer Street, Suite 3900, Halifax, Nova Scotia, Canada B3H 3A7.
J Magn Reson. 2012 Mar;216:152-60. doi: 10.1016/j.jmr.2012.01.017. Epub 2012 Feb 4.
This work proposes the use of TurboSPI, a multi-echo single point imaging sequence, for the quantification of labeled cells containing moderate to high concentrations of iron oxide contrast agent. At each k-space location, TurboSPI acquires several hundred time points during a spin echo, permitting reliable relaxation rate mapping of large-R(2)(∗) materials. An automatic calibration routine optimizes image quality by promoting coherent alignment of spin and stimulated echoes throughout the multi-echo train, and this calibration is sufficiently robust for in vivo applications. In vitro relaxation rate measurements of SPIO-loaded cervical cancer cells exhibit behavior consistent with theoretical predictions of the static dephasing regime in the spin echo case; the relaxivity measured with TurboSPI was 10.47±2.3 s(-1)/mG, comparable to the theoretical value of 10.78 s(-1)/mG. Similar measurements of micron-sized iron oxide particles (0.96 μm and 1.63 μm diameter) show a reduced relaxivity of 8.06±0.68 s(-1)/mG and 7.13±0.31 s(-1)/mG respectively, indicating that the static dephasing criterion was not met. Nonetheless, accurate quantification of such particles is demonstrated up to R(2)(∗)=900 s(-1), with a potentially higher upper limit for loaded cells having a more favorable R(2)('):R(2) ratio. Based on the cells used in this study, reliable quantification of cells loaded with 10 pg of iron per cell should be possible up to a density of 27 million cells/mL. Such quantification will be of crucial importance to the development of longitudinal monitoring for cellular therapy and other procedures using iron-labeled cells.
本研究提出使用 TurboSPI(一种多回波单点成像序列)对含有中高浓度氧化铁对比剂的标记细胞进行定量。在每个 k 空间位置,TurboSPI 在自旋回波期间获取数百个时间点,从而能够可靠地对大 R2*(弛豫率的平方)物质进行弛豫率映射。自动校准程序通过促进多回波序列中自旋和激发回波的相干对准来优化图像质量,这种校准对于体内应用来说足够稳健。SPIO 负载宫颈癌细胞的体外弛豫率测量结果与自旋回波情况下静态去相位的理论预测一致;用 TurboSPI 测量的弛豫率为 10.47±2.3 s(-1)/mG,与理论值 10.78 s(-1)/mG 相当。对微米级氧化铁颗粒(0.96 μm 和 1.63 μm 直径)的类似测量显示弛豫率分别降低至 8.06±0.68 s(-1)/mG 和 7.13±0.31 s(-1)/mG,表明未满足静态去相位标准。尽管如此,仍能对这些颗粒进行准确的定量,直到 R2=900 s(-1),负载细胞具有更有利的 R2('):R2 比值时,潜在的上限更高。基于本研究中使用的细胞,对于每细胞负载 10 pg 铁的细胞,应该能够可靠地定量高达 2700 万细胞/mL 的细胞密度。这种定量对于细胞治疗和其他使用铁标记细胞的程序的纵向监测的发展至关重要。