临床 3T MRI 扫描仪上肝癌的细胞外 pH 测绘。
Extracellular pH mapping of liver cancer on a clinical 3T MRI scanner.
机构信息
Department of Radiology & Biomedical Imaging, Yale University, New Haven, Connecticut.
Department of Biomedical Engineering, Yale University, New Haven, Connecticut.
出版信息
Magn Reson Med. 2020 May;83(5):1553-1564. doi: 10.1002/mrm.28035. Epub 2019 Nov 5.
PURPOSE
To demonstrate feasibility of developing a noninvasive extracellular pH (pH ) mapping method on a clinical MRI scanner for molecular imaging of liver cancer.
METHODS
In vivo pH mapping has been demonstrated on preclinical scanners (e.g., 9.4T, 11.7T) with Biosensor Imaging of Redundant Deviation in Shifts (BIRDS), where the pH readout by 3D chemical shift imaging (CSI) depends on hyperfine shifts emanating from paramagnetic macrocyclic chelates like TmDOTP which upon extravasation from blood resides in the extracellular space. We implemented BIRDS-based pH mapping on a clinical 3T Siemens scanner, where typically diamagnetic H signals are detected using millisecond-long radiofrequency (RF) pulses, and H shifts span over ±10 ppm with long transverse (T , 10 ms) and longitudinal (T , 10 ms) relaxation times. We modified this 3D-CSI method for ultra-fast acquisition with microsecond-long RF pulses, because even at 3T the paramagnetic H shifts of TmDOTP have millisecond-long T and T and ultra-wide chemical shifts (±200 ppm) as previously observed in ultra-high magnetic fields.
RESULTS
We validated BIRDS-based pH in vitro with a pH electrode. We measured pH in a rabbit model for liver cancer using VX2 tumors, which are highly vascularized and hyperglycolytic. Compared to intratumoral pH (6.8 ± 0.1; P < 10 ) and tumor's edge pH (6.9 ± 0.1; P < 10 ), liver parenchyma pH was significantly higher (7.2 ± 0.1). Tumor localization was confirmed with histopathological markers of necrosis (hematoxylin and eosin), glucose uptake (glucose transporter 1), and tissue acidosis (lysosome-associated membrane protein 2).
CONCLUSION
This work demonstrates feasibility and potential clinical translatability of high-resolution pH mapping to monitor tumor aggressiveness and therapeutic outcome, all to improve personalized cancer treatment planning.
目的
证明在临床 MRI 扫描仪上开发非侵入性细胞外 pH（pH）映射方法用于肝癌分子成像的可行性。
方法
在临床 3T 西门子扫描仪上实现了基于 Biosensor Imaging of Redundant Deviation in Shifts（BIRDS）的 pH 映射，其中通过 3D 化学位移成像（CSI）读出的 pH 值取决于超精细位移，这些超精细位移源自顺磁大环螯合物（如 TmDOTP），这些螯合物从血液中渗出后存在于细胞外空间。我们在临床 3T 西门子扫描仪上实现了基于 BIRDS 的 pH 映射，在该扫描仪中，通常使用毫秒长的射频（RF）脉冲检测抗磁性 H 信号，并且 H 位移跨越±10 ppm，具有长横向（T2，10ms）和纵向（T1，10ms）弛豫时间。我们修改了这种 3D-CSI 方法，使其具有微秒长的 RF 脉冲进行超快速采集，因为即使在 3T 下，TmDOTP 的顺磁 H 位移也具有毫秒级的 T1 和 T2 和超宽的化学位移（±200 ppm），如在超高磁场中先前观察到的那样。
结果
我们使用 pH 电极验证了基于 BIRDS 的 pH 值。我们使用 VX2 肿瘤（高度血管化和高糖酵解）在兔肝癌模型中测量了 pH 值。与肿瘤内 pH（6.8±0.1；P<10）和肿瘤边缘 pH（6.9±0.1；P<10）相比，肝实质 pH 值显著更高（7.2±0.1）。肿瘤定位通过坏死的组织学标志物（苏木精和伊红）、葡萄糖摄取（葡萄糖转运蛋白 1）和组织酸中毒（溶酶体相关膜蛋白 2）得到确认。
结论
这项工作证明了高分辨率 pH 映射监测肿瘤侵袭性和治疗效果的可行性和潜在临床转化能力，所有这些都旨在改善癌症个体化治疗计划。
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