Kuhlpeter Rebecca, Dahnke Hannes, Matuszewski Lars, Persigehl Thorsten, von Wallbrunn Angelika, Allkemper Thomas, Heindel Walter L, Schaeffter Tobias, Bremer Christoph
Department of Clinical Radiology, University Hospital of Muenster, Albert-Schweitzer-Str 33, D-48129, Muenster, Germany.
Radiology. 2007 Nov;245(2):449-57. doi: 10.1148/radiol.2451061345. Epub 2007 Sep 11.
To prospectively determine the cellular iron uptake by using R2 and R2* mapping with multiecho readout gradient-echo and spin-echo sequences.
All experiments were approved by the institutional animal care committee. Lung carcinoma cells were lipofected with superparamagnetic iron oxides (SPIOs). Agarose gel phantoms containing (a) 1 x 10(5) CCL-185 cells per milliliter of agarose gel with increasing SPIO load (0.01-5.00 mg of iron per milliliter in the medium), (b) different amounts (5.0 x 10(3) to 2.5 x 10(5) cells per milliliter of agarose gel) of identically loaded cells, and (c) free (non-cell-bound) SPIOs at the iron concentrations described for (b) were analyzed with 3.0-T R2 and R2* relaxometry. Iron uptake was analyzed with light microscopy, quantified with atomic emission spectroscopy (AES), and compared with MR data. For in vivo relaxometry, agarose gel pellets containing SPIO-labeled cells, free SPIO, unlabeled control cells, and pure agarose gel were injected into three nude mice each. Linear and nonlinear regression analyses were performed.
Light microscopy and AES revealed efficient SPIO particle uptake (mean uptake: 0.22 pg of iron per cell +/- 0.1 [standard deviation] for unlabeled cells, 31.17 pg of iron per cell +/- 4.63 for cells incubated with 0.5 mg/mL iron). R2 and R2* values were linearly correlated with cellular iron load, number of iron-loaded cells, and content of freely dissolved iron (r(2) range, 0.92-0.99; P < .001). For cell-bound SPIO, R2* effects were significantly greater than R2 effects (P < .01); for free SPIO, R2 and R2* effects were similar. In vivo relaxometry enabled accurate prediction of the number of labeled cells. R2' (R2* - R2) mapping enabled differentiation between cell-bound and free iron in vitro and in vivo.
Quantitative R2 and R2* mapping enables noninvasive estimations of cellular iron load and number of iron-labeled cells. Cell-bound SPIOs can be differentiated from free SPIOs with R2' imaging.
利用多回波读出梯度回波和自旋回波序列的R2和R2* 成像，前瞻性地确定细胞铁摄取情况。
所有实验均经机构动物护理委员会批准。用超顺磁性氧化铁（SPIO）对肺癌细胞进行脂质转染。对含有（a）每毫升琼脂糖凝胶中含1×10⁵个CCL - 185细胞且SPIO负载量不断增加（培养基中铁含量为0.01 - 5.00 mg/mL）、（b）不同数量（每毫升琼脂糖凝胶中含5.0×10³至2.5×10⁵个细胞）的等量负载细胞以及（c）（b）中所述铁浓度的游离（非细胞结合）SPIO的琼脂糖凝胶体模，采用3.0 T的R2和R2* 弛豫测量法进行分析。通过光学显微镜分析铁摄取情况，用原子发射光谱法（AES）进行定量，并与磁共振数据进行比较。对于体内弛豫测量，将含有SPIO标记细胞、游离SPIO、未标记对照细胞和纯琼脂糖凝胶的琼脂糖凝胶小球分别注入三只裸鼠体内。进行线性和非线性回归分析。
光学显微镜和AES显示SPIO颗粒摄取有效（未标记细胞的平均摄取量：每细胞0.22 pg铁±0.1[标准差]，与0.5 mg/mL铁孵育的细胞每细胞31.17 pg铁±4.63）。R2和R2* 值与细胞铁负载量、铁负载细胞数量以及游离溶解铁含量呈线性相关（r²范围为0.92 - 0.99；P <.001）。对于细胞结合的SPIO，R2* 效应显著大于R2效应（P <.01）；对于游离SPIO, R2 和R2* 效应相似。体内弛豫测量能够准确预测标记细胞的数量。R2'（R2* - R2）成像能够在体外和体内区分细胞结合铁和游离铁。
定量R2和R2* 成像能够无创估计细胞铁负载量和铁标记细胞数量。通过R2' 成像可区分细胞结合的SPIO和游离的SPIO。
