From the Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School.
Division of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA.
Invest Radiol. 2021 Apr 1;56(4):244-251. doi: 10.1097/RLI.0000000000000737.
Three groups of mice that develop either mild type 2 inflammation and fibrosis (wild type), severe fibrosis with exacerbated type 2 inflammation (Il10-/-Il12b-/-Il13ra2-/-), or minimal fibrosis with marked type 1 inflammation (Il4ra∂/∂) after infection with S. mansoni were imaged using both probes for determination of signal enhancement. Schistosoma mansoni-infected wild-type mice developed chronic liver fibrosis.
The liver MR signal enhancement after either probe administration was significantly higher in S. mansoni-infected wild-type mice compared with naive animals. The S. mansoni-infected Il4ra∂/∂ mice presented with little liver signal enhancement after probe injection despite the presence of substantial inflammation. Schistosoma mansoni-infected Il10-/-Il12b-/-Il13ra2-/- mice presented with marked fibrosis, which correlated to increased signal enhancement after injection of either probe.
Both MR probes, EP-3533 and Gd-Hyd, were specific for fibrosis in this model of chronic liver disease regardless of the presence or severity of the underlying inflammation. These results, in addition to previous findings, show the potential application of both molecular MR probes for detection and quantification of fibrosis from various etiologies.
三组感染曼氏血吸虫后发生 2 型轻度炎症和纤维化(野生型)、严重纤维化伴 2 型炎症加重(Il10-/-Il12b-/-Il13ra2-/-)或 1 型炎症明显伴轻度纤维化(Il4ra∂/∂)的小鼠,用两种探针进行成像以确定信号增强。曼氏血吸虫感染的野生型小鼠发生慢性肝纤维化。
与未感染动物相比,两种探针给药后,曼氏血吸虫感染的野生型小鼠的肝 MR 信号增强均显著升高。尽管存在大量炎症,探针注射后 Il4ra∂/∂感染的曼氏血吸虫小鼠肝脏信号增强很少。曼氏血吸虫感染的 Il10-/-Il12b-/-Il13ra2-/-小鼠表现出明显的纤维化,这与两种探针注射后的信号增强增加相关。
无论基础炎症的存在与否及其严重程度如何,两种 MR 探针 EP-3533 和 Gd-Hyd 在这种慢性肝病模型中均对纤维化具有特异性。除了先前的发现,这些结果表明这两种分子 MR 探针具有从各种病因检测和定量纤维化的潜在应用。