Ruo-Mi Guo

MR Neurography: T1 and T2 Measurements in Acute Peripheral Nerve Traction Injury in Rabbits

PURPOSE To prospectively evaluate magnetic resonance (MR) signal abnormalities and the time course of T1 and T2 values in a rabbit model of acute nerve traction injury with histologic and functional recovery correlation. MATERIALS AND METHODS All experimental protocols were approved by the institutional animal use and care committee. Acute traction injury was produced in the sciatic nerve of one hind limb in each of 28 rabbits. The contralateral sham-operated nerves served as controls. Sequential MR imaging and T1 and T2 measurements, as well as measurements of functional changes, were obtained over a 70-day follow-up period, with histologic assessments performed at regular intervals. Signal abnormalities and the time course of T1 and T2 values were observed in the proximal, traction, and distal portions of the injured nerves and the sham-operated nerves, and were compared with each other. RESULTS Nerves with acute traction injury showed visible hyperintense signals on T2-weighted images and had prolonged T1 and T2 values. Differences of T1 and T2 values were dependent on the sites along the same injured nerve, with the most pronounced and prolonged phase of T1 and T2 increases (peak values of 1333 msec +/- 46 and 79 msec +/- 3.7, respectively) observed in the most severely damaged portion of the injured nerve. T1 and T2 values and functional changes after nerve injury showed a similar time course. A return of T1 and T2 signals to normal values correlated with functional improvement. CONCLUSION MR imaging could be used to help predict the degree of nerve damage and monitor the process of nerve recovery in acute peripheral nerve traction injury. (c) RSNA, 2010.

Simultaneous diagnosis and gene therapy of immuno-rejection in rat allogeneic heart transplantation model using a T-cell-targeted theranostic nanosystem.

As the final life-saving treatment option for patients with terminal organ failure, organ transplantation is far from an ideal solution. The concomitant allograft rejection, which is hardly detectable especially in the early acute rejection (AR) period characterized by an intense cellular and humoral attack on donor tissue, greatly affects the graft survival and results in rapid graft loss. Based on a magnetic resonance imaging (MRI)-visible and T-cell-targeted multifunctional polymeric nanocarrier developed in our lab, effective co-delivery of pDNA and superparamagnetic iron oxide nanoparticles into primary T cells expressing CD3 molecular biomarker was confirmed in vitro. In the heart transplanted rat model, this multifunctional nanocarrier showed not only a high efficiency in detecting post-transplantation acute rejection but also a great ability to mediate gene transfection in T cells. Upon intravenous injection of this MRI-visible polyplex of nanocarrier and pDNA, T-cell gathering was detected at the endocardium of the transplanted heart as linear strongly hypointense areas on the MRI T(2)*-weighted images on the third day after cardiac transplantation. Systematic histological and molecular biology studies demonstrated that the immune response in heart transplanted rats was significantly suppressed upon gene therapy using the polyplex bearing the DGKα gene. More excitingly, the therapeutic efficacy was readily monitored by noninvasive MRI during the treatment process. Our results revealed the great potential of the multifunctional nanocarrier as a highly effective imaging tool for real-time and noninvasive monitoring and a powerful nanomedicine platform for gene therapy of AR with high efficiency.

Peripheral Nerve Repair: Monitoring by Using Gadofluorine M–enhanced MR Imaging with Chitosan Nerve Conduits with Cultured Mesenchymal Stem Cells in Rat Model of Neurotmesis

PURPOSE To observe the longitudinal changes of nerve repair in rats after tissue-engineered construct implantation at magnetic resonance (MR) imaging and to determine whether the enhanced nerve regeneration with use of tissue-engineered constructs could be monitored with gadofluorine M-enhanced MR imaging or nerve T2 relaxation time measurement. MATERIALS AND METHODS All experimental protocols were approved by the institutional Animal Use and Care Committee. Tissue-engineered constructs were prepared by seeding mesenchymal stem cells (MSCs) into chitosan nerve tubes. Thirty-six rats with sciatic nerve transection injury underwent nerve tube implantation with (n = 18) or without (n = 18) MSC seeding. Sequential T2 measurement, gadofluorine M-enhanced MR imaging, and sciatic function index measurement were performed over an 8-week follow-up period, with histologic assessments performed at regular intervals. T2 relaxation times and signal intensity at gadofluorine M-enhanced T1-weighted imaging were measured and were compared by using repeated-measures analysis of variance followed by the Student-Neuman-Keuls post-hoc test for multiple pairwise comparisons. RESULTS Nerve T2 relaxation times and gadofluorine M enhancement, as well as functional changes, showed a similar time course. Nerves implanted with MSC-seeded tubes achieved slightly better functional recovery and enhanced nerve regeneration while showing a slower return to baseline T2 relaxation time and a more rapid decline in gadofluorine M enhancement compared with nerves implanted with chitosan tubes alone. T2 values of the distal portion of transected nerves showed a more rapid return to baseline level than did gadofluorine M enhancement. CONCLUSION Peripheral nerve repair with use of tissue-engineered constructs can be monitored by using gadofluorine M-enhanced MR imaging and T2 relaxation time measurements. T2 relaxation time seems more sensitive than gadofluorine M-enhanced MR imaging for detecting nerve regeneration.

In vivo MR imaging tracking of transplanted mesenchymal stem cells in a rabbit model of acute peripheral nerve traction injury

To investigate in vivo MRI tracking mesenchymal stem cells (MSCs) in peripheral nerve injures using a clinically available paramagnetic contrast agent (Gd‐DTPA) and commercially available rhodamine‐incorporated transfection reagents (PEI‐FluoR).

Transplanted Neural Stem Cells Promote Nerve Regeneration in Acute Peripheral Nerve Traction Injury: Assessment Using MRI

OBJECTIVE The purpose of our study was to monitor neural stem cells (NSCs) transplanted in acute peripheral nerve traction injury and to use MRI to assess the ability of NSCs to promote nerve regeneration. MATERIALS AND METHODS After labeling with gadolinium-diethylene triamine pentaacetic acid (gadopentetate dimeglumine) and fluorescent dye (PKH26), 5 × 10(5) NSCs were grafted to acutely distracted sciatic nerves in 21 New Zealand White rabbits. In addition, 5 × 10(5) unlabeled NSCs (n = 21) and vehicle alone (n = 21) subjects were injected as a control. Serial MRI was performed with a 1.5-T scanner to determine the distribution of grafted cells. Sequential T1 and T2 values of the nerves and functional recovery were measured over a 70-day follow-up period, with histologic assessments performed at regular intervals. RESULTS The distribution and migration of labeled NSCs could be tracked with MRI until 10 days after transplantation. Compared with vehicle control, nerves grafted with labeled or unlabeled NSCs had better functional recovery and showed improved nerve regeneration but exhibited a sustained increase of T1 and T2 values during the phase of regeneration. CONCLUSION Gadopentetate dimeglumine-based labeling allowed short-term in vivo MRI tracking of NSCs grafted in injured nerves. NSCs transplantation could promote nerve regeneration in acute peripheral nerve traction injury as shown by a prolonged increase of nerve T1 and T2 values.

Efficient in vitro labeling rabbit neural stem cell with paramagnetic Gd-DTPA and fluorescent substance

OBJECTIVES The aim of this study is to label rabbit neural stem cells (NSCs) by using standard contrast agents (Gd-DTPA) in combination with PKH26 and in vitro track them with MR imaging. MATERIALS AND METHODS NSCs from prenatal brains of rabbits were cultured and propagated. Intracellular uptake of Gd-DTPA was achieved by using a non-liposomal lipid transfection reagent (Effectene) as the transfection agent. After labeling with Gd-DTPA, cells were incubated with cellular membrane fluorescent dye PKH26. The labeling effectiveness and the longevity of Gd-DTPA maintenance were measured on a 1.5T MR scanner. The influence of labeling on the cellular biological behaviors was assessed by cellular viability, proliferation and differentiation assessment. RESULTS The labeling efficiency of Gd-DTPA was up to 90%. The signal intensity on T1-weighted imaging and T1 values of labeled cells were significantly higher than those of unlabeled cells (P<0.05). The minimal number of detectable cells for T1-weighted imaging was 5×10(3). Cellular uptake of Gd-DTPA was maintained until 15 days after initially labeling. There was no significant difference in the cellular viability and proliferation between the labeled and unlabeled NSCs (P>0.05). Normal glial and neuronal differentiation remained in labeled NSCs like unlabeled NSCs. CONCLUSION Highly efficient labeling NSCs with Gd-DTPA could be achieved by using Effectene. This method of labeling NSCs allows for tracking cells with MR imaging, and without alterations of cellular biological behaviors.

Intraspinal primitive neuroectodermal tumor: Imaging findings in six cases

PURPOSE To retrospectively review CT and MRI findings in a series of six intraspinal primitive neuroectoderal tumors and to find out their radiological features. METHODS CT and MRI of six patients with surgically and pathologically proved intraspinal primitive neuroectoderal tumor were retrospectively reviewed. The tumor location, morphological features, signal intensity, calcification, contrast enhancement characteristics, involvement of paraspinal soft tissues and adjacent bony structures were assessed. RESULTS Of six patients, four had extradural lesions and two had intradural, extramedullary lesions. Most lesions were well defined and manifested heterogeneous iso- or hypo-intense signal on T1-weighted imaging and hyper-intense signal on T2-weighted imaging and moderate attenuation on CT, and were heterogeneously enhanced after contrast enhancement. The lesion extending through the intervertebral foramen with a large paraspinal soft tissue mass formed was found in four patients and vertebral bone involvement was seen in four patients. CONCLUSIONS Although imaging findings are not specific of intraspinal primitive neuroectoderal tumor, this diagnosis could be suggested when MR imaging depicts an intradural, extramedullary or extradural large well-circumscribed mass which extends out from intervertebral foramen and invades paraspinal soft tissues or vertebral bones in a young patient.

Theranostical nanosystem-mediated identification of an oncogene and highly effective therapy in hepatocellular carcinoma

Because the primary surgical treatment options for hepatocellular carcinoma (HCC)—including hepatic resection and liver transplantation—often fail due to recurrence and metastasis, identifying early prognostic biomarkers and therapeutic targets for HCC is of great importance. This study shows that transducin β‐like protein 1–related protein (TBLR1) is a key HCC oncogene that plays important roles in HCC proliferation, antiapoptosis, and angiogenesis by regulating the Wnt/β‐catenin pathway. The folate‐targeted theranostic small interfering RNA (siRNA) nanomedicine Fa‐PEG‐g‐PEI‐SPION/psiRNA‐TBLR1 effectively silences the TBLR1 gene in different human HCC cell lines in vitro and in human HCC samples in vivo, resulting in the simultaneous suppression of HCC cell proliferation, antiapoptosis, and angiogenesis. Because of its multi‐anticancer functions against HCC, intravenous injection of the folate‐targeted siRNA nanomedicine into nude mice bearing intrahepatic or subcutaneous xenografts of human HCC has a significant therapeutic effect. Tumor growth in those animals was almost completely inhibited by treatment with Fa‐PEG‐g‐PEI‐SPION/psiRNA‐TBLR1. Moreover, the SPION‐encapsulated polyplexes possess high magnetic resonance imaging (MRI) detection sensitivity, which makes tumor‐targeted siRNA delivery easily trackable using the clinical MRI technique. Conclusion: The theranostic siRNA nanomedicine examined here possesses great theranostic potential for combined gene therapy and MRI diagnosis of HCC. (Hepatology 2016;63:1240–1255)

A Stable Focal Cerebral Ischemia Injury Model in Adult Mice: Assessment Using 7T MR Imaging

BACKGROUND AND PURPOSE: A stable stroke experimental model is highly desirable for performing longitudinal studies using MR imaging. The purpose of this study is to establish a stable focal cerebral ischemia model with a high survival rate in adult mice. MATERIALS AND METHODS: One hundred twenty adult mice were randomly divided into 10 groups of 12 each to respectively undergo intraluminal suture occlusion, with suture insertion depths from 0.8 cm to maximum; thromboembolic occlusion; and hypoxic-ischemic injury with hypoxia exposure times from 30–120 minutes. Coronal brain T2-weighted images were obtained on a 7T scanner. The induced infarct volume and location were assessed and correlated with histologic TTC staining. One-day and 7-day survival rates were recorded. RESULTS: The infarct location was highly variable in the thromboembolic model, while it showed a cortex predominance in the intraluminal model with the suture insertion depth ≥1.4 cm, and the HI model with hypoxia exposure times ≥60 minutes (P = .001). The infarct volume in the intraluminal model with suture depths ≥1.4 cm (29.7 ± 3.3%, 35.4 ± 4.3%) and the HI model with the hypoxia exposure times ≥90 minutes (26.3 ± 4.1%, 33.4 ± 2.8%) were larger than other groups (9.7 ± 3.3%–20.9 ± 9.3%; P < .05). The HI group (72.5%) had higher 7-day survival rate than the intraluminal suture occlusion (28%) and thromboembolic occlusion groups (20%; P = .001). CONCLUSIONS: The HI injury model with a reproducible ishemia and high survival rate can be used for a longitudinal study of brain ischemia in adult mice.

In vivo MRI monitoring nerve regeneration of acute peripheral nerve traction injury following mesenchymal stem cell transplantation

OBJECTIVE To assess the continuous process of nerve regeneration in acute peripheral nerve traction injury treated with mesenchymal stem cells (MSCs) transplantation using MRI. MATERIALS AND METHODS 1 week after acute nerve traction injury was established in the sciatic nerve of 48 New Zealand white rabbits, 5×10(5) MSCs and vehicle alone were grafted to the acutely distracted sciatic nerves each in 24 animals. Serial MRI and T1 and T2 measurements of the injured nerves were performed with a 1.5-T scanner and functional recovery was recorded over a 10-week follow-up period, with histological assessments performed at regular intervals. RESULTS Compared with vehicle control, nerves grafted with MSCs had better functional recovery and showed improved nerve regeneration, with a sustained increase of T1 and T2 values during the phase of regeneration. CONCLUSION MRI could be used to monitor the enhanced nerve regeneration in acute peripheral nerve traction injury treated with MSC transplantation, reflected by a prolonged increase in T1 and T2 values of the injured nerves.