Xiaohui Duan

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.

Magnetic Resonance Imaging of Mesenchymal Stem Cells Labeled with Dual (MR and Fluorescence) Agents in Rat Spinal Cord Injury

RATIONALE AND OBJECTIVES In vivo tracking cells using gadolinium-based contrast agents have the important advantage of providing a positive contrast on T1-weighted images, which is less likely to be confused with artifacts because of postoperative local signal voids such as metal, hemorrhage, or air. The aim of this study is to paramagnetically and fluorescently label marrow with dual agents (gadolinium-diethylene triamine penta-acetic acid [Gd-DTPA] and PEI-FluoR) and track them after transplantation into spinal cord injury (SCI) with magnetic resonance imaging (MRI). MATERIALS AND METHODS Marrow mesenchymal stem cells (MSCs) from Sprague-Dawley rats were incubated with PEI-FluoR (rhodamine-conjugated PEI-FluoR) and Gd-DTPA complex for labeling. After labeling, cellular viability, proliferation, and apoptosis were evaluated. T1 value and longevity of intracellular Gd-DTPA retention were measured on a 1.5 T MRI scanner. Thirty-six SCI rats were implanted with labeled and unlabeled MSCs and phosphate-buffered saline. Then, serial MRI and Basso-Beattie-Bresnehan (BBB) locomotor tests were performed and correlated with fluorescent microscopy. The relative signal intensity (RSL) of the engraftment in relation to normal cord was measured and the linear mixed model followed by post-hoc Bonferroni test was used to identify significant differences in RSL as well as BBB score. RESULTS MSCs could be paramagnetically and fluorescently labeled by the dual agents. The labeling did not influence the cellular viability, proliferation, and apoptosis. The longevity of Gd-DTPA retention in labeled MSCs was up to 21 days. The distribution and migration of labeled MSCs in SCI lesions could be tracked until 7 days after implantation on MRI. The relative signal intensities of SCI rats treated with labeled cells at 1 day and 3 days (1.34 +/- 0.02, 1.27 +/- 0.03) were significantly higher than rats treated with unlabeled cells (0.94 +/- 0.01, 0.99 +/- 0.02) and phosphate-buffered saline (0.91 +/- 0.01, 0.95 +/- 0.01) (P < .05). Rats treated with labeled MSCs or unlabeled MSCs achieved significantly higher BBB scores than controls at 14, 21, 28, and 35 days after injury (P < .05). CONCLUSIONS Labeling MSCs with the dual agents may enable cellular MRI and tracking in experimental spinal cord injury.

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.

A novel polymeric micelle used for in vivo MR imaging tracking of neural stem cells in acute ischemic stroke

Transplantation of neural stem cells (NSCs) is a promising treatment strategy for acute ischemic stroke. In vivo tracking of the therapeutic stem cells in the host brain after transplantation is essential not only to ensure the safety and efficacy of the treatment, but also to better understand their migrational dynamics and regeneration potential. Many polymeric nanoparticles have been developed to label stem cells for in vivo tracking by magnetic resonance imaging (MRI), optical imaging (OI) or other imaging modalities. However, the non-degradability and presence of cellular toxicity of the nanoparticles restrict their clinical applications. In this study, we developed a novel cationic polymeric micelles based on amphipathic polymer of biodegradable hydrophilic poly(aspartic acid-dimethylethanediamine) (PAsp(DMA)) that were conjugated with two molecules of hydrophobic cholic acid (CA) by lysine. Image labels, superparamagnetic iron oxide nanoparticles (SPIONs) and fluorescent nile red were simultaneously loaded into the micelles to label NSCs. The labeling capacity, efficiency and cytotoxicity of the cationic micelles were determined. The in vivo MRI tracking of the therapeutic NSCs in acute ischemic stroke was also explored. Our results showed that this type of cationic polymeric micelles achieved a high efficient and safe labeling of NSCs and resulted in reliable in vivo MRI tracking of therapeutic stem cells in acute ischemic stroke, but without detrimental effect. The cationic, biodegradable polymeric micelles are highly translatable for clinical application and can be used as a versatile nanoplatform for stem cell labeling and subsequently in vivo tracking in regenerative medicine.

Superparamagnetic Iron Oxide Nanoparticles-Complexed Cationic Amylose for In Vivo Magnetic Resonance Imaging Tracking of Transplanted Stem Cells in Stroke

Cell-based therapy with mesenchymal stem cells (MSCs) is a promising strategy for acute ischemic stroke. In vivo tracking of therapeutic stem cells with magnetic resonance imaging (MRI) is imperative for better understanding cellular survival and migrational dynamics over time. In this study, we develop a novel biocompatible nanocomplex (ASP-SPIONs) based on cationic amylose, by introducing spermine and the image label, ultrasmall superparamagnetic iron oxide nanoparticles (SPIONs), to label MSCs. The capacity, efficiency, and cytotoxicity of the nanocomplex in transferring SPIONs into green fluorescence protein-modified MSCs were tested; and the performance of in vivo MRI tracking of the transplanted cells in acute ischemic stroke was determined. The results demonstrated that the new class of SPIONs-complexed nanoparticles based on biodegradable amylose can serve as a highly effective and safe carrier to transfer magnetic label into stem cells. A reliable tracking of transplanted stem cells in stroke was achieved by MRI up to 6 weeks, with the desirable therapeutic benefit of stem cells on stroke retained. With the advantages of a relatively low SPIONs concentration and a short labeling period, the biocompatible complex of cationic amylose with SPIONs is highly translatable for clinical application. It holds great promise in efficient, rapid, and safe labeling of stem cells for subsequent cellular MRI tracking in regenerative medicine.

In Vivo Targeted Magnetic Resonance Imaging of Endogenous Neural Stem Cells in the Adult Rodent Brain

Neural stem cells in the adult mammalian brain have a significant level of neurogenesis plasticity. In vivo monitoring of adult endogenous NSCs would be of great benefit to the understanding of the neurogenesis plasticity under normal and pathological conditions. Here we show the feasibility of in vivo targeted MR imaging of endogenous NSCs in adult mouse brain by intraventricular delivery of monoclonal anti-CD15 antibody conjugated superparamagnetic iron oxide nanoparticles. After intraventricular administration of these nanoparticles, the subpopulation of NSCs in the anterior subventricular zone and the beginning of the rostral migratory stream could be in situ labeled and were in vivo visualized with 7.0-T MR imaging during a period from 1 day to 7 days after the injection. Histology confirmed that the injected targeted nanoparticles were specifically bound to CD15 positive cells and their surrounding extracellular matrix. Our results suggest that in vivo targeted MR imaging of endogenous neural stem cells in adult rodent brain could be achieved by using anti-CD15-SPIONs as the molecular probe; and this targeting imaging strategy has the advantage of a rapid in vivo monitoring of the subpopulation of endogenous NSCs in adult brains.

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.