Susceptibility-weighted imaging for stem cell visualization in a rat photothrombotic cerebral infarction model.

BACKGROUND: In cell therapy, magnetic resonance imaging (MRI) has been used to visualize superparamagnetic iron oxide (SPIO)-labeled stem cells homing to a lesion. Improving traceability is to utilize the sequence that maximizes sensitivity to the susceptibility effect of SPIO. PURPOSE: To explore the best method by comparing the MRI sequences to visualize mesenchymal stem cells (MSCs) labeled with SPIO. MATERIAL AND METHODS: Human bone marrow (hBM)-derived MSCs were labeled by internalization of SPIO nanoparticles. In vitro MRI was performed for the SPIO-labeled hBM-MSCs in tubes with T2-weighted (T2W), T2*-weighted (T2*W), and susceptibility-weighted images (SWI). Contrast-to-noise ratio (CNR) and volumes of dark signal of SPIO-labeled hBM-MSCs were obtained on images of each sequence. Photothrombotic cerebral infarction (PTCI) was induced in eight rats, and 2.5 × 10(5) SPIO-labeled hBM-MSCs were infused through the tail vein on the third day. In vivo MRI of the rat brain was performed using a 3.0 T MRI on the first, third, seventh, and 14th days. CNRspio was obtained on T2W imaging, T2*W imaging, and SWI. The dark signals were compared with the SPIO-positive cells of Prussian blue staining. RESULTS: In vitro MRI of 5 × 10(5) SPIO-labeled hBM-MSCs showed the CNR and volume of dark signal to be 63, 517 mm(3) in SWI, 41, 228 mm(3) in T2*W imaging, and 56, 41 mm(3) in T2W imaging, respectively. In vivo MRI showed a dark signal surrounding the high signal intensity of PTCI. Pathologically, the dark signals were matched with SPIO-labeled hBM-MSC in the corresponding rat. The dark signal was most prominent in SWI, then T2*W imaging, and finally in T2W imaging (P <0.05). In SWI, other causes of dark signals were matched with the veins and the choroid plexuses on histopathology. CONCLUSION: SWI can visualize SPIO-labeled hBM-MSCs more sensitively, earlier, and with larger size and greater contrast than T2W imaging and T2*W imaging.

Engraftment of human mesenchymal stem cells in a rat photothrombotic cerebral infarction model : comparison of intra-arterial and intravenous infusion using MRI and histological analysis.

OBJECTIVE: This study aimed to evaluate the hypotheses that administration routes [intra-arterial (IA) vs. intravenous (IV)] affect the early stage migration of transplanted human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in acute brain infarction. METHODS: Male Sprague-Dawley rats (n=40) were subjected to photothrombotic infarction. Three days after photothrombotic infarction, rats were randomly allocated to one of four experimental groups [IA group : n=12, IV group : n=12, superparamagnetic iron oxide (SPIO) group : n=8, control group : n=8]. All groups were subdivided into 1, 6, 24, and 48 hours groups according to time point of sacrifice. Magnetic resonance imaging (MRI) consisting of T2 weighted image (T2WI), T2(*) weighted image (T2(*)WI), susceptibility weighted image (SWI), and diffusion weighted image of rat brain were obtained prior to and at 1, 6, 24, and 48 hours post-implantation. After final MRI, rats were sacrificed and grafted cells were analyzed in brain and lung specimen using Prussian blue and immunohistochemical staining. RESULTS: Grafted cells appeared as dark signal intensity regions at the peri-lesional zone. In IA group, dark signals in peri-lesional zone were more prominent compared with IV group. SWI showed largest dark signal followed by T2(*)WI and T2WI in both IA and IV groups. On Prussian blue staining, IA administration showed substantially increased migration and a large number of transplanted hBM-MSCs in the target brain than IV administration. The Prussian blue-positive cells were not detected in SPIO and control groups. CONCLUSION: In a rat photothrombotic model of ischemic stroke, selective IA administration of human mesenchymal stem cells is more effective than IV administration. MRI and histological analyses revealed the time course of cell migration, and the numbers and distribution of hBM-MSCs delivered into the brain.