From the Institute of Experimental Neurology (INSPE) and Experimental Imaging Center (CIS), INSPE-DiBiT2, IRCCS Ospedale San Raffaele, via Olgettina 60, Milan 20132, Italy (C.C., D.D.B., G.C., L.C.); and SupraBioNano Laboratory, Department of Chemistry, Materials, and Chemical Engineering "Giulio Natta" Politecnico di Milano, Milan, Italy (I.T., P.M., F.B.B.).
Radiology. 2019 May;291(2):351-357. doi: 10.1148/radiol.2019181073. Epub 2019 Mar 19.
Background MRI with fluorine 19 (F) probes has shown an ability to track immune cell activity with a specific, stable, and quantitative signal. In addition, the chemical shift differences of selected F probes make dual-probe imaging possible. To improve F MRI sensitivity for dual-probe imaging, optimal fluorine probes are needed. Purpose To develop multispectral F MRI to image immune cell activity in vivo using F nanoparticles of two distinct fluorocarbons. Materials and Methods Both F nanoparticles formulated with two fluorocarbons with distinct resonance frequencies and a high fluorine payload were characterized in terms of size, stability, MR profile, and relaxation times at 7 T. F MRI sensitivity was tested on labeling cells both in vitro and in vivo in C57BL/6 mice after conditional ablation of myeloid cells through the inhibition of colony-stimulating factor-1 receptor (CSF1Ri) to monitor the change of immune cells phagocytosis. Fluorine MRI data were acquired at the resonance frequency of each fluorocarbon by using a three-dimensional fast spin-echo sequence. Fluorescent dyes were also inserted into F nanoparticles to allow flow-cytometric and confocal microscopy analysis of labeled cells. Fluorine signal-to-noise ratio (SNR) was compared by using two-way repeated measures analysis of variance with Bonferroni post hoc correction. Results Fluorine MRI demonstrated high sensitivity and high specificity in the imaging of mononuclear cells both in vitro and in vivo. In combination with proton MRI, a map of F nuclei from each fluorocarbon was obtained without overlaps or artifacts. In vitro cell viability was unchanged, and 8000 cells with a high SNR (>8) were detected. In vivo high fluorine signal was observed in the bone marrow (SNR > 15) immediately after CSF1Ri treatment interruption, which correlated with high uptake by neutrophils and monocytes at flow cytometry. Conclusion By assessing in vivo MRI of mononuclear cell phagocytic ability with F nanoparticles, MRI with dual F probes can effectively track immune cell activity in combination with current MRI protocols. © RSNA, 2019 See also the editorial by Bulte in this issue.
背景 氟 19（F）探针的 MRI 已显示出具有特定、稳定和定量信号的能力，可用于跟踪免疫细胞的活性。此外，所选 F 探针的化学位移差异使得双探针成像成为可能。为了提高双探针成像的 F MRI 灵敏度，需要优化 F 探针。目的 开发多谱 F MRI，使用两种不同氟碳化合物的 F 纳米颗粒在体内成像免疫细胞活性。材料与方法 对两种具有不同共振频率和高氟载量的氟碳化合物制成的 F 纳米颗粒进行了大小、稳定性、MR 谱和弛豫时间的表征，并在 7T 下进行了测试。通过抑制集落刺激因子-1 受体（CSF1Ri）对髓样细胞进行条件性消融后，在体外和体内对标记细胞进行 F MRI 灵敏度测试，以监测免疫细胞吞噬作用的变化。通过使用三维快速自旋回波序列，在每个氟碳化合物的共振频率处采集氟 MRI 数据。还将荧光染料插入 F 纳米颗粒中，以便对标记细胞进行流式细胞术和共聚焦显微镜分析。通过使用双向重复测量方差分析和 Bonferroni 事后校正比较氟信号与噪声比（SNR）。结果 F MRI 显示在体外和体内单核细胞成像中具有高灵敏度和高特异性。与质子 MRI 结合，获得了来自每个氟碳化合物的 F 核的图谱，没有重叠或伪影。细胞活力无变化，体外检测到 8000 个具有高 SNR（>8）的细胞。CSF1Ri 治疗中断后，骨髓中立即观察到高氟信号（SNR>15），这与流式细胞术检测到中性粒细胞和单核细胞摄取量高相关。结论 通过使用 F 纳米颗粒评估单核细胞吞噬能力的体内 MRI，双 F 探针 MRI 可与当前的 MRI 方案有效结合，跟踪免疫细胞的活性。 由 RSNA 出版，2019 年 本期 Bulte 编辑的社论也可参见。
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