Rehabilitation facilitates functional improvement following intravenous infusion of mesenchymal stem cells in the chronic phase of cerebral ischemia in rats.

The primary objective of this study was to investigate the potential facilitating effects of daily rehabilitation for chronic cerebral ischemia following the intravenous infusion of mesenchymal stem cells (MSC) in rats. The middle cerebral artery (MCA) was occluded by intraluminal occlusion using a microfilament (MCAO). Eight weeks after MCAO induction, the rats were used as a chronic cerebral ischemia model. Four experimental groups were studied: Vehicle group (medium only, no cells); Rehab group (vehicle + rehabilitation), MSC group (MSC only); and Combined group (MSC + rehabilitation). Rat MSCs were intravenously infused eight weeks after MCAO induction, and the rats received daily rehabilitation through treadmill exercise for 20 min. Behavioral testing, lesion volume assessment using magnetic resonance imaging (MRI), and histological analysis were performed during the observation period until 16 weeks after MCAO induction. All treated animals showed functional improvement compared with the Vehicle group; however, the therapeutic efficacy was greatest in the Combined group. The combination therapy is associated with enhanced neural plasticity shown with histological analysis and MRI diffusion tensor imaging. These findings provide behavioral evidence for enhanced recovery by combined therapy with rehabilitation and intravenous infusion of MSCs, and may form the basis for the development of clinical protocols in the future.

Therapeutic efficacy of intravenous infusion of mesenchymal stem cells in rat perinatal brain injury.

BACKGROUND: Perinatal brain injury is multifactorial and primarily associated with brain prematurity, inflammation, and hypoxia-ischemia. Although recent advances in perinatal medicine　have improved the survival rates of preterm infants, neurodevelopmental disorders remain a significant complication. We tested whether the intravenous infusion of mesenchymal stem cells (MSCs) had therapeutic efficacy against perinatal brain injury in rats. METHODS: Pregnant rats at embryonic day (E) 18 received lipopolysaccharide and the pups were born at E21. On postnatal day (PND) 7, the left common carotid artery of each pup was ligated, and they were exposed to 8% oxygen for 2 h. They were randomized on PND10, and MSCs or vehicle were intravenously infused. We performed behavioral assessments, measured brain volume using MRI, and performed histological analyses on PND49. RESULTS: Infused MSCs showed functional improvements in our model. In vivo MRI revealed that MSC infusion increased non-ischemic brain volume compared to the vehicle group. Histological analyses showed that cortical thickness, the number of NeuN+ and GAD67+ cells, and synaptophysin density in the non-ischemic hemisphere in the MSC group were greater than the vehicle group, but less than the control group. CONCLUSIONS: Infused MSCs improve sensorimotor and cognitive functions in perinatal brain injury and enhance neuronal growth. IMPACT: Intravenous infusion of MSCs improved neurological function in rats with perinatal brain injury, including motor, sensorimotor, cognitive, spatial, and learning memory. Infused MSCs increased residual (non-ischemic) tissue volume, number of neuronal cells, GABAergic cells, and cortical synapses in the contralesional (right) hemisphere. Intravenous administration of MSC might be suitable for the treatment of perinatal brain injury.

Repeated intravenous infusion of mesenchymal stem cells enhances recovery of motor function in a rat model with chronic spinal cord injury.

Spinal cord injury (SCI) can cause paralysis with a high disease burden with limited treatment options. A single intravenous infusion of mesenchymal stem cells (MSCs) improves motor function in rat SCI models, possibly through the induction of axonal sprouting and remyelination. Repeated infusions (thrice at weekly intervals) of MSCs were administered to rats with chronic SCI to determine if multiple-dosing regimens enhance motor improvement. Chronic SCI rats were randomized and infused with vehicle (vehicle), single MSC injection at week 6 (MSC-1) or repeatedly injections of MSCs at 6, 7, and 8 weeks (MSC-3) after SCI induction. In addition, a single high dose of MSCs (HD-MSC) equivalent to thrice the single dose was infused at week 6. Locomotor function, light and electron microscopy, immunohistochemistry and ex vivo diffusion tensor imaging were performed. Repeated infusion of MSCs (MSC-3) provided the greatest functional recovery compared to single and single high-dose infusions. The density of remyelinated axons in the injured spinal cord was the greatest in the MSC-3 group, followed by the MSC-1, HD-MSC and vehicle groups. Increased sprouting of the corticospinal tract and serotonergic axon density was the greatest in the MSC-3 group, followed by MSC-1, HD-MSC, and vehicle groups. Repeated infusion of MSCs over three weeks resulted in greater functional improvement than single administration of MSCs, even when the number of infused cells was tripled. MSC-treated rats showed axonal sprouting and remyelination in the chronic phase of SCI.

Computational Fluid Dynamics Analysis Features in Aneurysm Development in Rats.

The investigation of how to control the development and growth of cerebral aneurysms is important for the prevention of subarachnoid hemorrhage. Although there have been several types of research studies on computational fluid dynamics (CFD) analysis of brain aneurysm development and growth, there has been no unified interpretation of the CFD analysis results. The purpose of this study is to clarify the characteristics of CFD analysis results related to the development of cerebral aneurysms using an animal model. Nineteen rat models of cerebral aneurysms were created, and the CFD analysis results between the cerebral aneurysm group [n = 10; the aneurysm was observed on magnetic resonance angiography (MRA) within 10 weeks after aneurysm induction surgery] and the nonaneurysm group (n = 9) were compared. All aneurysms were confirmed on the proximal segment of the left cerebral artery (P1), and the cross-sectional area and curvature of the left P1 were evaluated together. In the cerebral aneurysm group, there was a decrease in wall shear stress (WSS) that is consistent with the location of the aneurysm compared to the nonaneurysm group. The cross-sectional area of the left P1 gradually increased in the aneurysm group but not in the nonaneurysm group. The mean curvature in the entire left P1 was higher in the aneurysm group than in the nonaneurysm group. This study revealed that the development of cerebral aneurysms is due to changes in vascular morphology, namely, an increase in vessel diameter and a high curvature, and a decreased WSS consistent with the site of aneurysm development using this animal model.

Accuracy of computed tomography: magnetic resonance imaging image fusion using a phantom for skull base surgery.

BACKGROUND: The aim of this study is to assess the positional accuracy of image fusions of the skull base region using different magnetic resonance imaging (MRI) and computed tomography (CT) image pairs. METHODS: An image set of 3D fast imaging employing steady-state acquisition-C (FIESTA-C) was used as the base image set. Image fusions were performed using an image set with different fields of view (FOVs): one with different matrix size, one with a different sequence of 3D spoiled gradient recalled acquisition, and one with different modality (CT), using a phantom including multi columnar objects. Position of columns at the center, and 4 and 8 cm from the center were measured. The displacements between the base image set and fused image set were measured. For slices with different z-positions, the displacement of the 8-cm column was assessed. For 20 clinical MRI cases, the distance between the dorsum sellae and the cranial nerves was measured. RESULTS: No significant differences were found between the different FOVs or image sequences. However, with the different matrix sizes and modalities, significant displacements were observed, although they were all within 0.5 mm. Similar displacements were observed in the slices at different z-positions. All cranial nerves were located within 40 mm of the dorsum sellae. CONCLUSIONS: The displacements following image fusion were within approximately 0.5 mm, even at 8 cm from the center. This suggests that the region where the cranial nerves are located, within 40 mm of the dorsum sellae, had no risk of positional error following image fusion.

Intravenous Infusion of Mesenchymal Stem Cells Enhances Therapeutic Efficacy of Reperfusion Therapy in Cerebral Ischemia.

OBJECTIVE: Reperfusion therapy is a standard therapeutic strategy for acute stroke. Non-favorable outcomes are thought to partially result from impaired microcirculatory flow in ischemic tissue. Intravenous infusion of mesenchymal stem cells (MSCs) reduces stroke volume and improves behavioral function in stroke. One suggested therapeutic mechanism is the restoration of the microvasculature. The goal of this study was to determine whether infused MSCs enhance the therapeutic efficacy of reperfusion therapy following stroke in rats. METHODS: First, to establish a transient middle cerebral artery occlusion (MCAO) model displaying approximately identical neurologic function and lesion volume as seen in permanent MCAO (pMCAO) at day 7 after stroke induction, we transiently occluded the MCA for 90, 110, and 120 minutes. We found that the 110-minute occlusion met these criteria and was used as the transient MCAO (tMCAO) model. Next, 4 MCAO groups were used to compare the therapeutic efficacy of infused MSCs: (1) pMCAO+vehicle, (2) tMCAO+vehicle, (3) pMCAO+MSC, and (4) tMCAO+MSC. Our ischemic model was a unique ischemic model system in which both pMCAO and tMCAO provided similar outcomes during the study period in the groups without MSC infusion groups. Behavioral performance, ischemic volume, and regional cerebral blood flow (rCBF) using arterial spin labeling-magnetic resonance imaging and histologic evaluation of microvasculature was performed. RESULTS: The behavioral function, rCBF, and restoration of microvasculature were greater in group 4 than in group 3. Thus, infused MSCs facilitated the therapeutic efficacy of MCA reperfusion in this rat model system. CONCLUSIONS: Intravenous infusion of MSCs may enhance therapeutic efficacy of reperfusion therapy.

Visualization of cerebellar peduncles using diffusion tensor imaging.

The cerebellum communicates with the cerebral cortex via the superior, middle, and inferior cerebellar peduncles (CPs). To preserve the structure and function of the brainstem and cerebellum, which is compressed in various pathological conditions, it is important to delineate the spatial interrelationship of the CPs for presurgical planning and intraoperative guidance. Diffusion tensor tractography (DTT) is a technique capable of depicting the major fiber bundles in CPs. However, routine use of this technology for brainstem visualization remains challenging due to the anatomical smallness and complexity of the brainstem and susceptibility-induced image distortions. Here, we attempt to visualize CPs using high-resolution DTT in a commercial equipment for the application of this technique in normal clinical settings. DTT and fast imaging employing steady-state acquisition-cycled phases (FIESTA) of the whole brainstem were performed. We rendered the DTT fiber bundle using a region-of-interest-based fiber tracking method onto the structural image generated in FIESTA by automatic image coregistration. Fibers of the CPs were clearly visualized by DTT. The DTT-FIESTA overlaid image revealed the cross-sectional and three-dimensional anatomy of the pyramidal tract and the ascending sensory fibers, in addition to the CPs. This could indicate a geometrical relationship of these fibers in the brainstem. The CPs could be visualized clearly using DTT within clinically acceptable scanning times. This method of visualizing the exact pathway of fiber bundles and cranial nerves in the skull base helps in the planning of surgical approaches.

Intravenous delivery of mesenchymal stem cells protects both white and gray matter in spinal cord ischemia.

Ischemic spinal cord injury (iSCI) is a devastating complication of aortic surgery, with few strategies for prevention. Intravenous infusion of mesenchymal stem cells (MSCs) for iSCI has been shown to provide functional improvement through protection of gray matter. The purpose of this study was to investigate additional mechanisms which may exert therapeutic efficacy in iSCI. Severe iSCI was created to occlude the descending aorta, which was cross-clamped 5 mm distal to the left subclavian artery for 16 min. One day after iSCI induction, iSCI rats were randomized into two groups: one received intravenous infusion of MSCs (MSC-group), the other received vehicle (no cells; vehicle-group). Locomotor function and in vivo MRI were recorded. H&E, Nissl and toluidine blue stainings, immunohistochemical analysis, diffusion tensor imaging (DTI), and the assessment of blood-spinal cord barrier (BSCB) stability were performed. MSC treated animals exhibited gradual improvement in hind-limb locomotor function during the 4-week study period; however the vehicle-treated group displayed persistent motor deficits. In the MSC-treated group we observed the protection of white and gray matter volume reduction of axonal and neuronal loss or degeneration and preservation of microvasculature including BSCB function. Intravenous infusion of MSCs may provide therapeutic efficacy to improve functional outcomes in a rat model of severe iSCI via protection of white and gray matter.

Intravenous infusion of mesenchymal stem cells improves impaired cognitive function in a cerebral small vessel disease model.

Cerebral small vessel disease (CSVD) is not only a cause of vascular dementia (VD) but also a contributing factor to Alzheimer's disease (AD). The essential pathological feature of CSVD is the disruption of blood-brain barrier (BBB). Dysfunction of BBB due to degeneration of both endothelial cells and pericytes in capillaries leads to neuronal damage and progressive brain atrophy. Moreover, deterioration of amyloid-ß (Aß) clearance due to the failure of the transvascular BBB transport system results in accumulation of Aß in the brain. Intravenous infusion of mesenchymal stem cells (MSCs) elicits functional recovery in experimental models including stroke and spinal cord injury. One effect of MSCs is to restore disrupted BBB through remodeling of microvasculature. Using spontaneously hypertensive rats (stroke-prone) with impaired cognitive function as a CSVD model, we have shown that infused MSCs has a therapeutic effect for cognitive function. Restoration of BBB function via remodeling of microvasculature and inhibition of Aß accumulation could inhibit progressive brain atrophy and lead to restore cognitive dysfunction. Gene expression analysis indicated that infused MSCs activates both transforming growth factor-ß and angiopoietin 1 signaling pathways and promotes the remodeling of microvasculature. Thus, infused MSCs may represent a novel therapy for both VD and AD.

Elevated brain derived neurotrophic factor levels in plasma reflect in vivo functional viability of infused mesenchymal stem cells for stroke in rats.

BACKGROUND: Intravenous infusion of mesenchymal stem cells (MSCs) derived from adult bone marrow elicits functional recovery in rat stroke models and clinical studies in patients are ongoing. Brain derived neurotrophic factor (BDNF) is a neurotrophic factor produced by MSCs and may contribute to their therapeutic efficacy. The purpose of the current study was to determine if BDNF is elevated in infarcted brain and in which compartment of blood (plasma or serum) after intravenous MSC infusion in a middle cerebral artery occlusion (MCAO) model in the rat. METHODS: In rats, a permanent middle cerebral artery occlusion (MCAO) was induced by intraluminal vascular occlusion with a microfilament and MSCs were intravenously administered 6 h after right MCAO induction. Enzyme-linked immunosorbent assay (ELISA) analysis of brain, serum and plasma BDNF were performed after the MSC infusion following the MCAO induction. Lesion volume was assessed using magnetic resonance imaging. Functional outcome was assessed using the Limb Placement Test. RESULTS: Infused MSCs reduced lesion volume and elicited functional improvement compared to the vehicle infused group. ELISA analysis of the MSC treated group revealed an increase BDNF levels in the infarcted hemisphere of the brain and plasma, but not in serum. The MSC group showed a greater increase in BDNF levels than sham control. In the MSC group, the expression of increased plasma BDNF levels correlated with increased brain BDNF levels. CONCLUSIONS: These results support the hypothesis that BDNF levels in plasma, but not serum, may be more appropriate to detect circulating BDNF in vivo following MSC infusion in a cerebral infarction rat model of ischemic stroke. Further, plasma BDNF might reflect in vivo functional viability of infused MSCs after stroke.

Intravenous infusion of mesenchymal stem cells for protection against brainstem infarction in a persistent basilar artery occlusion model in the adult rat.

OBJECTIVE: Morbidity and mortality in patients with posterior circulation stroke remains an issue despite advances in acute stroke therapies. The intravenous infusion of mesenchymal stem cells (MSCs) elicits therapeutic efficacy in experimental supratentorial stroke models. However, since there are few reliable animal models of ischemia in the posterior circulation, the therapeutic approach with intravenous MSC infusion has not been tested. The objective of this study was to test the hypothesis that intravenously infused MSCs provide functional recovery in a newly developed model of brainstem infarction in rats. METHODS: Basilar artery (BA) occlusion (BAO) was established in rats by selectively ligating 4 points of the proximal BA with 10-0 nylon monofilament suture. The intravenous infusion of MSCs was performed 1 day after BAO induction. MRI and histological examinations were performed to assess ischemic lesion volume, while multiple behavioral tests were performed to evaluate functional recovery. RESULTS: The MSC-treated group exhibited a greater reduction in ischemic lesion volume, while behavioral testing indicated that the MSC-infused group had greater improvement than the vehicle group 28 days after the MSC infusion. Accumulated infused MSCs were observed in the ischemic brainstem lesion. CONCLUSIONS: Infused MSCs may provide neuroprotection to facilitate functional outcomes and reduce ischemic lesion volume as evaluated in a newly developed rat model of persistent BAO.

Intravenous infusion of mesenchymal stem cells promotes functional recovery in a rat model of chronic cerebral infarction.

OBJECTIVE: Intravenous infusion of mesenchymal stem cells (MSCs) derived from adult bone marrow improves behavioral function in rat models of cerebral infarction. Although clinical studies are ongoing, most studies have focused on the acute or subacute phase of stroke. In the present study, MSCs derived from bone marrow of rats were intravenously infused 8 weeks after the induction of a middle cerebral artery occlusion (MCAO) to investigate whether delayed systemic injection of MSCs improves functional outcome in the chronic phase of stroke in rats. METHODS: Eight weeks after induction of the MCAO, the rats were randomized and intravenously infused with either MSCs or vehicle. Ischemic volume and behavioral performance were examined. Blood-brain barrier (BBB) integrity was assessed by quantifying the leakage of Evans blue into the brain parenchyma after intravenous infusion. Immunohistochemical analysis was also performed to evaluate the stability of the BBB. RESULTS: Motor recovery was better in the MSC-treated group than in the vehicle-treated group, with rapid improvement (evident at 1 week post-infusion). In MSC-treated rats, reduced BBB leakage and increased microvasculature/repair and neovascularization were observed. CONCLUSIONS: These results indicate that the systemic infusion of MSCs results in functional improvement, which is associated with structural changes in the chronic phase of cerebral infarction, including in the stabilization of the BBB.

Preservation of interhemispheric cortical connections through corpus callosum following intravenous infusion of mesenchymal stem cells in a rat model of cerebral infarction.

Systemic administration of mesenchymal stem cells (MSCs) following cerebral infarction exerts functional improvements. Previous research has suggested potential therapeutic mechanisms that promote neuroprotection and synaptogenesis. These include secretion of neurotrophic factors, remodeling of neural circuits, restoration of the blood brain barrier, reduction of inflammatory infiltration and demyelination, and elevation of trophic factors. In addition to these mechanisms, we hypothesized that restored interhemispheric bilateral motor cortex connectivity might be an additional mechanism of functional recovery. In the present study, we have shown, with both MRI diffusion tensor imaging (DTI) and neuroanatomical tracing techniques using an adeno-associated virus (AAV) expressing GFP, that there was anatomical restoration of cortical interhemispheric connections through the corpus callosum after intravenous infusion of MSCs in a rat middle cerebral artery occlusion (MCAO) stroke model. Moreover, the degree of connectivity was greater in the MSC-treated group than in the vehicle-infused group. In accordance, both the thickness of corpus callosum and synaptic puncta in the contralateral (non-infarcted) motor cortex connected to the corpus callosum were greater in the MSC-treated group than in the vehicle group. Together, these results suggest that distinct preservation of interhemispheric cortical connections through corpus callosum was promoted by intravenous infusion of MSCs. This anatomical preservation of the motor cortex in the contralateral hemisphere may contribute to functional improvements following MSC therapy for cerebral stroke.

Intravenous infusion of mesenchymal stem cells reduces epileptogenesis in a rat model of status epilepticus.

OBJECTIVE: Status epilepticus (SE) causes neuronal cell death, aberrant mossy fiber sprouting (MFS), and cognitive deteriorations. The present study tested the hypothesis that systemically infused mesenchymal stem cells (MSCs) reduce epileptogenesis by inhibiting neuronal cell death and suppressing aberrant MFS, leading to cognitive function preservation in a rat model of epilepsy. METHODS: SE was induced using the lithium-pilocarpine injection model. The seizure frequency was scored using a video-monitoring system and the Morris water maze test was carried out to evaluate cognitive function. Comparisons were made between MSCs- and vehicle-infused rats. Immunohistochemical staining was performed to detect Green fluorescent protein (GFP)+ MSCs and to quantify the number of GAD67+ and NeuN+ neurons in the hippocampus. Manganese-enhanced magnetic resonance imaging (MEMRI) and Timm staining were also performed to assess the MFS. RESULTS: MSC infusion inhibited epileptogenesis and preserved cognitive function after SE. The infused GFP+ MSCs were accumulated in the hippocampus and were associated with the preservation of GAD67+ and NeuN+ hippocampal neurons. Furthermore, the MSC infusion suppressed the aberrant MFS in the hippocampus as evidenced by MEMRI and Timm staining. CONCLUSIONS: This study demonstrated that the intravenous infusion of MSCs mitigated epileptogenesis, thus advancing MSCs as an effective approach for epilepsy in clinical practice.

Intravenous infusion of mesenchymal stem cells inhibits intracranial hemorrhage after recombinant tissue plasminogen activator therapy for transient middle cerebral artery occlusion in rats.

OBJECTIVE Reperfusion therapy with intravenous recombinant tissue plasminogen activator (rtPA) is the standard of care for acute ischemic stroke. However, hemorrhagic complications can result. Intravenous infusion of mesenchymal stem cells (MSCs) reduces stroke volume and improves behavioral function in experimental stroke models. One suggested therapeutic mechanism is inhibition of vascular endothelial dysfunction. The objective of this study was to determine whether MSCs suppress hemorrhagic events after rtPA therapy in the acute phase of transient middle cerebral artery occlusion (tMCAO) in rats. METHODS After induction of tMCAO, 4 groups were studied: 1) normal saline [NS]+vehicle, 2) rtPA+vehicle, 3) NS+MSCs, and 4) rtPA+MSCs. The incidence rate of intracerebral hemorrhage, both hemorrhagic and ischemic volume, and behavioral performance were examined. Matrix metalloproteinase-9 (MMP-9) levels in the brain were assessed with zymography. Quantitative analysis of regional cerebral blood flow (rCBF) was performed to assess hemodynamic change in the ischemic lesion. RESULTS The MSC-treated groups (Groups 3 and 4) experienced a greater reduction in the incidence rate of intracerebral hemorrhage and hemorrhagic volume 1 day after tMCAO even if rtPA was received. The application of rtPA enhanced activation of MMP-9, but MSCs inhibited MMP-9 activation. Behavioral testing indicated that both MSC-infused groups had greater improvement than non-MSC groups had, but rtPA+MSCs provided greater improvement than MSCs alone. The rCBF ratio of rtPA groups (Groups 2 and 4) was similar at 2 hours after reperfusion of tMCAO, but both were greater than that in non-rtPA groups. CONCLUSIONS Infused MSCs may inhibit endothelial dysfunction to suppress hemorrhagic events and facilitate functional outcome. Combined therapy of infused MSCs after rtPA therapy facilitated early behavioral recovery.

Intravenous infusion of mesenchymal stem cells promotes functional recovery in a model of chronic spinal cord injury.

Intravenous infusion of mesenchymal stem cells (MSCs) derived from adult bone marrow improves behavioral function in rat models of spinal cord injury (SCI). However, most studies have focused on the acute or subacute phase of SCI. In the present study, MSCs derived from bone marrow of rats were intravenously infused 10weeks after the induction of a severe contusive SCI. Open field locomotor function was assessed weekly until 20weeks post-SCI. Motor recovery was greater in the MSC-treated group with rapid improvement beginning in earlier post-infusion times than in the vehicle-treated group. Blood spinal cord barrier (BSCB) integrity was assessed by the intravenous infusion of Evans Blue (EvB) with spectrophotometric quantitation of its leakage into the parenchyma. In MSC-treated rats, BSCB leakage was reduced. Immunohistochemical staining for RECA-1 and PDGFR-ß showed increased microvasculature/repair-neovascularization in MSC-treated rats. There was extensive remyelination around the lesion center and increased sprouting of the corticospinal tract and serotonergic fibers after MSC infusion. These results indicate that the systemic infusion of MSCs results in functional improvement that is associated with structural changes in the chronically injured spinal cord including stabilization of the BSCB, axonal sprouting/regeneration and remyelination.

Synergic Effects of Rehabilitation and Intravenous Infusion of Mesenchymal Stem Cells After Stroke in Rats.

BACKGROUND: Intravenous infusion of mesenchymal stem cells (MSCs) derived from adult bone marrow improves behavioral function in rat stroke models. Rehabilitation therapy through physical exercise also provides therapeutic efficacy for cerebral ischemia. OBJECTIVE: The purpose of this study was to investigate whether synergic effects of daily rehabilitation and intravenous infusion of MSCs has therapeutic effects after stroke in rats. DESIGN: This was an experimental study. METHODS: A permanent middle cerebral artery occlusion (MCAO) was induced by intraluminal vascular occlusion with a microfilament. Four experimental groups were studied: group 1 (vehicle only, n=10), group 2 (vehicle + exercise, n=10), group 3 (MSCs only, n=10), and group 4 (MSCs + exercise, n=10). Rat MSCs were intravenously infused at 6 hours after MCAO, and the rats received daily rehabilitation with treadmill running exercise for 20 minutes. Lesion size was assessed at 1, 14, and 35 days using magnetic resonance imaging. Functional outcome was assessed using the Limb Placement Test. RESULTS: Both combined therapy and MSC infusion reduced lesion volume, induced synaptogenesis, and elicited functional improvement compared with the groups without MSC infusion, but the effect was greater in the combined therapy group. LIMITATIONS: A limitation of this study is that the results were limited to an animal model and cannot be generalized to humans. CONCLUSIONS: The data indicate that the combined therapy of daily rehabilitation and intravenous infusion of MSCs improved functional outcome in a rat MCAO model.

MRI of Perfusion: Principles and Clinical Applications.

The principle and clinical application of measurement of cerebral blood perfusion (CBP) using MRI are described. Purposes of measuring CBP using MRI are wide-ranging. Generally, it is used to diagnose cerebro-vascular disorders or brain tumors. There are two types of measuring methods. One is dynamic susceptibility contrast (DSC) method using a contrast agent as a tracer. Another is an arterial spin labeling (ASL) method using protons in arterial blood as an endogenous tracer, instead of bio-exogenous tracer. Basic theory of ASL method was published in the 1990s, recently, its clinical application has been spreading rapidly by the technological innovations. ASL method is attractive as a way to measure CBP because of its non-invasiveness (no radiation-exposure, not need intravenous injection or blood sampling), and the imaging time is about 5 minutes, thereby the measurement can be repeated. The analysis of DSC method has not been standardized, though various valuable parameters are provided. And the prerequisite of DSC method is uncertain in vivo. On the other hand, the result of ASL is affected by the post labeling delay, and limited to the arterial information.

[Optimized magnetic resonance sequences and parameters with operative assisted images for radical prostatectomy at 3 tesla-magnetic resonance image].

The objective of our study was to optimize magnetic resonance image (MRI) sequences and parameters using operative assisted images (three-dimensional images) for radical prostatectomy at 3 tesla (T) MRI. Five healthy volunteers underwent MRI on the 3.0 T scanner. Various sequences and parameters [Cube (TE/TR = 18, 50, 90 ms/2000 ms), FIESTA (TE/TR/FA = 2.4 ms/5 ms/40 degrees, 90 degrees), fSPGR (TE/TR/FA = 2.3 ms/11.2 ms/20 degrees), slice thickness = 1.2 mm, matrix = 192 x 160] were respectively compared. Several structures of the pelvis (the central zones and transition zones of the prostate, the peripheral zones of the prostate, seminal vesicles, rectum wall, bladder, muscle and fat) were determined. The signal intensities of these structures were measured on reformatted axial images and compared against several structures of the pelvis. Correlation with various sequences and parameters was based on the signal-to-noise ratio (SNR), the contrast ratio (CR) and the presence of artifacts. Student's t-test was used for statistical analysis. With Cube (TE/TR = 50 ms/2000 ms), the average value of visual evaluation with artifacts was high, and SNR and CR were higher than for other sequence and parameters. Optimized MRI sequences and parameters were Cube (TE/TR = 50 ms/2000 ms) which provides improved SNR and CR and the presence of artifacts with operative assisted images for radical prostatectomy. These operative assisted images obtained from Cube (TE/TR = 50 ms/2000 ms) are likely to be useful for surgery.