Magnetic resonance cholangiopancreatography (MRCP) is widely accepted for visualization of the biliary system. However, the sensitivity and specificity of MRCP for the diagnosis of biliary atresia (BA) are still not fully elucidated. This study aimed to investigate the diagnostic value of three-dimensional MRCP (3D-MRCP) for BA in a large cohort of cholestatic infants and neonates. One hundred ninety patients with infant jaundice underwent 3D-MRCP and one or more of the following: (1) intraoperative cholangiography, (2) laparoscopic exploration and pathological examination, or/and (3) clinical therapy. Statistical analyses were performed to determine the diagnostic accuracy of 3D-MRCP for BA. Our study demonstrated that 158 of 190 patients were interpreted as having BA by 3D-MRCP; of those, 103 patients were confirmed as having BA, whereas 55 patients did not have BA. Of the 32 patients interpreted as non-BA cases by 3D-MRCP, one patient was misdiagnosed. The diagnostic accuracy for 3D-MRCP was 70.53% (134 of 190), the sensitivity was 99.04% (103 of 104), the specificity was 36.05% (31 of 86), the negative predictive value was 96.88% (31 of 32), the positive predictive value was 65.19% (103 of 158), the positive likelihood ratio was 2.7473, the negative likelihood ratio was 0.0267, and the Youden index was 0.3509. The sensitivity of 3D-MRCP in diagnosing BA was excellent, but the specificity was not as high as described in previous reports. 3D-MRCP can be an effective screening method but should be combined with other modalities to identify BA and distinguish it from other causes of infant jaundice.

Introduction: Despite the strong appeal of ferritin as a magnetic resonance imaging (MRI) reporter for stem cell research, no attempts have been made to apply this genetic imaging reporter in stem cells in an inducible manner, which is important for minimizing the potential risk related to the constitutive expression of an imaging reporter. The aim of the present study was to develop an inducible genetic MRI reporter system that enables the production of intracellular MRI contrast as needed. Methods: Ferritin heavy chain (FTH1) was genetically modified by adding a Tet-On switch. A C3H10T1/2 cell line carrying Tet-FTH1 (C3H10T1/2-FTH1) was established via lentiviral transduction. The dose- and time-dependent expression of FTH1 in C3H10T1/2 cells was assessed by western blot and immunofluorescence staining. The induced “ON” and non-induced “OFF” expressions of FTH1 were detected using a 3.0 T MRI scanner. Iron accumulation in cells was analyzed by Prussian blue staining and transmission electron microscopy (TEM). Results: The expression of FTH1 was both dose- and time-dependently induced, and FTH1 expression peaked in response to induction with doxycycline (Dox) at 0.2 μg/ml for 72 h. The induced expression of FTH1 resulted in a significant increase in the transverse relaxation rate of C3H10T1/2-FTH1 cells following iron supplementation. Prussian blue staining and TEM revealed extensive iron accumulation in C3H10T1/2–FTH1 cells in the presence of Dox. Conclusions: Cellular MRI contrast can be produced as needed via the expression of FTH1 under the control of a Tet-On switch. This finding could lay the groundwork for the use of FTH1 to track stem cells in vivo in an inducible manner.

Background: Existing evidence has shown that mesenchymal stem cells (MSCs) can undergo malignant transformation, which is a serious limitation of MSC-based therapies. Therefore, it is necessary to monitor malignant transformation of MSCs via a noninvasive imaging method. Although reporter gene-based magnetic resonance imaging (MRI) has been successfully applied to longitudinally monitor MSCs, this technique cannot distinguish the cells before and after malignant transformation. Herein, we investigated the feasibility of using a tumor-specific promoter to drive reporter gene expression for MRI detection of the malignant transformation of MSCs. Methods: The reporter gene ferritin heavy chain (FTH1) was modified by adding a promoter from the tumor-specific gene progression elevated gene-3 (PEG3) and transduced into MSCs to obtain MSCs-PEG3-FTH1. Cells were induced to undergo malignant transformation via indirect coculture with C6 glioma cells, and these transformed cells were named MTMSCs-PEG3-FTH1. Western blot analysis of FTH1 expression, Prussian blue staining and transmission electron microscopy (TEM) to detect intracellular iron, and MRI to detect signal changes were performed before and after malignant transformation. Then, the cells before and after malignant transformation were inoculated subcutaneously into nude mice, and MRI was performed to observe the signal changes in the xenografts. Results: After induction of malignant transformation, MTMSCs demonstrated tumor-like features in morphology, proliferation, migration, and invasion. FTH1 expression was significantly increased in MTMSCs-PEG3-FTH1 compared with MSCs-PEG3-FTH1. Prussian blue staining and TEM showed a large amount of iron particles in MTMSCs-PEG3-FTH1 but a minimal amount in MSCs-PEG3-FTH1. MRI demonstrated that the T2 value was significantly decreased in MTMSCs-PEG3-FTH1 compared with MSCs-PEG3-FTH1. In vivo, mass formation was observed in the MTMSCs-PEG3-FTH1 group but not the MSCs-PEG3-FTH1 group. T2-weighted MRI showed a significant signal decrease, which was correlated with iron accumulation in the tissue mass. Conclusions: We developed a novel MRI model based on FTH1 reporter gene expression driven by the tumor-specific PEG3 promoter. This approach could be applied to sensitively detect the occurrence of MSC malignant transformation.