Christoforidis Gregory A, Yang Ming, Kontzialis Marinos S, Larson Douglas G, Abduljalil Amir, Basso Michelle, Yang Weilian, Ray-Chaudhury Abhik, Heverhagen Johannes, Knopp Michael V, Barth Rolf F
Department of Radiology, The Ohio State University Medical Center, Columbus, OH 43210, USA.
Invest Radiol. 2009 Jul;44(7):375-83. doi: 10.1097/RLI.0b013e3181a8afea.
This study assessed whether ultra-small particles of iron oxide (USPIO) intravascular contrast agent could enhance visualization of tumor microvascularity in F98 glioma bearing rats by means of ultra high field (UHF) high-resolution gradient echo (GRE) magnetic resonance imaging (MRI). In an effort to explain differences in visualization of microvascularity before and after USPIO administration, hypoxia and vessel diameters were assessed on corresponding histopathologic sections.
F98 glioma cells were implanted stereotactically into the brains of syngeneic Fischer rats. Based on clinical criteria, rats were imaged 1 to 2 days before their death with and without USPIO contrast on an 8 Tesla MRI. To identify hypoxic regions of the brain tumor by immunohistochemical staining, a subset of animals also received a nitroimidazole-based hypoxia marker, EF5, before euthanasia. These sections then were compared with noncontrast enhanced MR images. The relative caliber of tumor microvasculature, compared with that of normal brain, was analyzed in a third group of animals.
After USPIO administration, UHF high-resolution GRE MRI consistently predicted increased microvascular density relative to normal gray matter when correlated with histopathology. The in-plane visibility of glioma microvascularity in 22 rats increased by an average of 115% and signal intensity within the tumor decreased by 13% relative to normal brain. Tumor microvascularity identified on noncontrast MR images matched hypoxic regions identified by immunohistochemical staining with a sensitivity of 83% and specificity of 89%. UHF GRE MRI was able to resolve microvessels less than 20 micro in diameter, although differences in tumor vessel size did not consistently account for differences in visualization of microvascularity.
USPIO administration significantly enhanced visualization of tumor microvascularity on gradient echo 8 T MRI and significantly improved visualization of tumor microvascularity. Microvascularity identified on precontrast images is suspected to be partly associated with hypoxia.
本研究评估超小氧化铁颗粒（USPIO）血管内造影剂能否通过超高场（UHF）高分辨率梯度回波（GRE）磁共振成像（MRI）增强荷F98胶质瘤大鼠肿瘤微血管的可视化。为了解释USPIO给药前后微血管可视化的差异，对相应组织病理学切片进行了缺氧和血管直径评估。
将F98胶质瘤细胞立体定向植入同基因Fischer大鼠脑内。根据临床标准，在大鼠死亡前1至2天，使用8特斯拉MRI对其进行有无USPIO造影剂的成像。为通过免疫组织化学染色识别脑肿瘤的缺氧区域，一部分动物在安乐死之前还接受了基于硝基咪唑的缺氧标记物EF5。然后将这些切片与未增强造影剂的MR图像进行比较。在第三组动物中分析肿瘤微血管与正常脑微血管的相对管径。
给予USPIO后，与组织病理学相关时，UHF高分辨率GRE MRI始终预测相对于正常灰质微血管密度增加。22只大鼠的胶质瘤微血管在平面内的可见性平均增加了115%，肿瘤内的信号强度相对于正常脑降低了13%。未增强造影剂的MR图像上识别出的肿瘤微血管与免疫组织化学染色识别出的缺氧区域相匹配，灵敏度为83%，特异性为89%。UHF GRE MRI能够分辨直径小于20微米的微血管，尽管肿瘤血管大小的差异并不能始终解释微血管可视化的差异。
给予USPIO可显著增强梯度回波8T MRI上肿瘤微血管的可视化，并显著改善肿瘤微血管的可视化。造影前图像上识别出的微血管被怀疑部分与缺氧有关。
