Differences between Acute Embolic and Atherosclerotic Middle Cerebral Artery Occlusion in Multiphase Arterial Spin-labeling Imaging.

Arterial spin-labeling magnetic resonance imaging (ASL-MRI) is widely used for evaluating collateral development in patients with acute ischemic stroke (AIS). This study aimed to characterize the findings of multiphase ASL-MRI between embolic and atherosclerotic large vessel occlusion (LVO) to aid in the differential diagnosis. Among 982 patients with AIS, 44 who were diagnosed with acute, symptomatic, and unilateral occlusion of the horizontal segment of the middle cerebral artery (MCA) were selected and categorized into embolic stroke (ES) and atherosclerosis (AT) groups. Using ASL-MRI (postlabeling delay [PLD] of 1.5, 2.0, and 2.5 s) at admission, the ipsilateral to contralateral ratio (ICR) of the signal intensity and its time-course increasing rate (from PLD 1.5 to 2.0 and 2.5, ΔICR) were measured and compared between the two groups. The mean ICR was significantly higher in the AT group than in the ES group (AT vs. ES: 0.49 vs. 0.27 for ICR1.5, 0.73 vs. 0.32 for ICR2.0, and 0.92 vs. 0.37 for ICR2.5). The ΔICR of PLD 1.5-2.0 (ΔICR2.0) and 2.5 (ΔICR2.5) were also significantly higher in the AT group than in the ES group (AT vs. ES: 50.9% vs. 26.3% for ΔICR2.0, and 92.6% vs. 42.9% for ΔICR2.5). Receiver operating characteristic curves showed moderate-to-strong discriminative abilities of each ASL-MRI parameter in predicting MCA occlusion etiology. In conclusion, multiphase ASL-MRI parameters may aid in differentiating intracranial LVO etiology during the acute phase. Thus, it is applicable to AIS management.

Low b-value Diffusion Tensor Imaging to Analyze the Dynamics of Cerebrospinal Fluid: Resolving Intravoxel Pseudorandom Motion into Ordered and Disordered Motions.

PURPOSE: Analysis of cerebrospinal fluid (CSF) dynamics may be beneficial for understanding the mechanisms and diagnosis of several neurological diseases. Low b-value diffusion tensor imaging (low-b DTI) is useful for observing the slow and complex motion of the CSF. Theoretically, a mathematical framework suggests that low-b DTI provides the variance of the pseudorandom motion of the CSF. Furthermore, low-b DTI could provide comprehensive information on fluid dynamics. Accordingly, we proposed an analysis technique that resolves intravoxel pseudorandom motion into ordered (linear) and disordered (random) motions based on the mathematical framework. METHODS: The proposed analysis technique helps measure low-b DTI with multiple diffusion times and linearly fits its mean diffusivity (MD) with the diffusion time to obtain two parameters, double-slope Vv and y-intersect Dr, which represent the variance of the velocity distribution of linear motion and the diffusion coefficient of random motion, respectively. Seven healthy subjects were scanned to evaluate the proposed technique and investigate fluid dynamics in several representative ROIs. RESULTS: The obtained data showed the validity of the technique, repeatability, and consistency across the subjects in ROIs, such as the lateral ventricle (LV), third ventricle (3V), fourth ventricle (4V), and Sylvian fissure (SF). The obtained parameters Vv and Dr highlighted different characteristics of fluid dynamics in the representative ROIs: low Vv and low Dr in the LV, high Vv and moderate Dr in the 3V, and moderate Vv and moderate Dr in the 4V and SF. CONCLUSION: The proposed analysis technique will facilitate a comprehensive investigation of the complex dynamics of the CSF using resolved parameters representing ordered and disordered motions.

Case report: Self-restraint in a patient with alien hand syndrome following cerebral infarction involving the anterior cerebral artery territory.

Frontal alien hand syndrome (AHS) presents as impulsive grasping and groping and compulsive manipulation of environmental objects that can affect the dominant or nondominant hand. A few reports have shown improvements in neuropsychological scores over time when self-restraint of the right hand AHS was enforced. A 72-year-old woman presented with right-handed involuntary instinctive grasping reactions and compulsive manipulation of tools after an infarction of the frontal lobe and corpus callosum (CC). She was diagnosed with cerebral infarction involving the anterior cerebral artery territory and a frontal variant of AHS. At AHS onset, the patient was unaware that her right hand was moving against her will; she was only aware that her right hand was moving when the therapist pointed it out to her. Later, she began to recognize that her right hand was involuntarily moving, and she could restrain the movement of her right hand with her left hand. Approximately 5 months following AHS onset, the patient could voluntarily restrain her AHS symptoms by telling her right hand not to move against her will in her head. Most neuropsychological scores improved by 5 months following AHS onset. However, the patient showed disruptions in the genu and midbody of the left cingulate cortex, as shown via diffusion tensor imaging (DTI), and the sensation of the "right hand moving by itself" remained even 5 months after AHS onset. Although damage to the CC fibers was evident on DTI at 5 months following onset, the patient exhibited no sensory deficits and demonstrated good hand ownership as well as early improvement in attention and cognitive dysfunction. Therefore, the patient recognized her AHS symptoms, which included her hand moving against her will, and was able to consciously restrain her hand movement.

Low b-value diffusion tensor imaging for measuring pseudorandom flow of cerebrospinal fluid.

PURPOSE: Cerebrospinal fluid (CSF) plays an important role in the clearance system of the brain. Recently, low b-value diffusion tensor imaging (low-b DTI) has been reported to be useful in the observation of CSF flow; however, the precise flow property observed by low-b DTI has not been fully investigated. Accordingly, a mathematical framework of low-b DTI is proposed for investigating CSF and clarifying its pseudorandom flow. THEORY: The framework will show that the limit of the diffusion tensor as b-value decreases to zero approximately represents the covariance of the velocity distribution of the CSF's pseudorandom flow. METHODS: The low b-value diffusion tensor (DTL ) of whole-brain CSF was obtained using diffusion-weighted echo-planar imaging. Seven healthy volunteers were scanned for intersubject analysis; three of the volunteers was consecutively scanned for repeatability analysis. Obtained DTL was visually assessed by ellipsoid-representation map and was statistically evaluated by calculating mean diffusivity (MD) and fractional anisotropy (FA) in regions of interest (ROIs) representing intensive pseudorandom flow. RESULTS: Obtained DTL consistently shows large and anisotropic diffusivity in some segments of CSF, typically the ROIs around the foramen of Monro, the aqueduct, the prepontine cistern, the middle cerebral artery, and the Sylvian fissure throughout the study. The statistical analysis shows high repeatability and consistently high MD and FA in all the ROIs for all the volunteers. CONCLUSION: From the viewpoint of the proposed framework, the high and anisotropic DTL in the ROIs indicates large covariance of velocity distribution, which represents intensive pseudorandom flows of CSF.

Utility of Radial Scanning for the Identification of Arterial Hypervascularity of Hepatocellular Carcinoma on Gadoxetic Acid-Enhanced Magnetic Resonance Images.

OBJECTIVES: This study aimed to compare the accuracy of assessing the arterial hypervascularity of hepatocellular carcinoma (HCC) on dynamic computed tomography (CT) scans and gadoxetic acid (EOB)-enhanced magnetic resonance imaging (MRI) scans performed with radial sampling. METHODS: We studied the images of 40 patients with hypervascular HCC. A radiologist recorded the standard deviation of the attenuation (or the signal intensity [SI]) in subcutaneous fat tissue as the image noise (N) and calculated the contrast-to-noise ratio (CNR) as follows: (CNR) = (n-ROIT - n-ROIL)/N, where n-ROIT is the mean attenuation (or SI) of the tumor divided by the mean attenuation (or SI) of the aorta and n-ROIL is the mean attenuation (or SI) of the liver parenchyma divided by the mean attenuation (or SI) of the aorta. RESULTS: The CNR was significantly higher on EOB-enhanced MRI than on dynamic CT scans. CONCLUSIONS: For the assessment of HCC vascularity, EOB-enhanced MRI scans acquired with radial sampling were more accurate than dynamic CT images.

Thickness dependent homogeneous crystallization of ultrathin amorphous solid water films.

The crystallization mechanism and kinetics of amorphous materials are of paramount importance not only in basic science but also in the application field because they are closely related to their thermal stability. In the case of amorphous nanomaterials, thermal stability distinctively different from that of bulk materials often emerges. Despite intensive studies in the past, a thorough understanding of the stability at the molecular level has not been reached particularly on how crystallization processes depend on size and are influenced by their surface and interface. In this article, we report the film-size-dependent crystallization of thermally relaxed nonporous ASW ultrathin films on a Pt(111) surface as a benchmark system of amorphous molecular films. The crystallization processes at the surface and interior of the ASW ultrathin films are monitored simultaneously with thermal desorption and infrared reflection absorption, respectively, as a function of the film thickness. Here, we demonstrate that the crystallization is initiated solely by "homogeneous nucleation" irrespective of the film thickness while the crystallization rate remarkably depends on the thickness; the rate of 5-layer (∼1.5 nm) ASW films is one order of magnitude higher than that of 20-layer (∼6 nm) films. Moreover, we found a clear correlation between the film-thickness-dependent crystallization kinetics and microscopic structural disorder associated with the broad distribution of hydrogen-bond lengths between water molecules.

Pseudo-random Trajectory Scanning Suppresses Motion Artifacts on Gadoxetic Acid-enhanced Hepatobiliary-phase Magnetic Resonance Images.

PURPOSE: Hepatobiliary-phase (HBP) MRI with gadoxetic acid facilitates the differentiation between lesions with and without functional hepatocytes. Thus, high-quality HBP images are required for the detection and evaluation of hepatic lesions. However, the long scan time may increase artifacts due to intestinal peristalsis, resulting in the loss of diagnostic information. Pseudo-random acquisition order disperses artifacts into the background. The aim of this study was to investigate the clinical applicability of pseudo-random trajectory scanning for the suppression of motion artifacts on T1-weighted images including HBP. METHODS: Our investigation included computer simulation, phantom experiments, and a clinical study. For computer simulation and phantom experiments a region of interest (ROI) was placed on the area with motion artifact and the standard deviation inside the ROI was measured as image noise. For clinical study we subjected 62 patients to gadoxetic acid-enhanced hepatobiliary-phase imaging with a circular- and a pseudo-random trajectory (c-HBP and p-HBP); two radiologists graded the motion artifacts, sharpness of the liver edge, visibility of intrahepatic vessels, and overall image quality using a five-point scale where 1 = unacceptable and 5 = excellent. Differences in the qualitative scores were determined using the two-sided Wilcoxon signed-rank test. RESULTS: The image noise was higher on the circular image compared with pseudo-random image (101.0 vs 60.9 on computer simulation image, 91.2 vs 67.7 on axial, 95.5 vs 86.9 on reformatted sagittal image for phantom experiments). For clinical study the score for motion artifacts was significantly higher with p-HBP than c-HBP imaging (left lobe: mean 3.4 vs 3.2, P < 0.01; right lobe: mean 3.6 vs 3.4, P < 0.01) as was the qualitative score for the overall image quality (mean 3.6 vs 3.3, P < 0.01). CONCLUSION: At gadoxetic acid-enhanced hepatobiliary-phase imaging, p-HBP scanning suppressed motion artifacts and yielded better image quality than c-HBP scanning.

Demonstration of Human Fetal Bone Morphology with MR Imaging: A Preliminary Study.

PURPOSE: CT is a useful modality for the evaluation of fetal skeletal dysplasia but radiation exposure is unavoidable. The purpose of this study is to compare the usefulness of MRI and CT for evaluating the fetal skeletal shape. METHODS: This study was approved by our Institutional Review Board. Fetal specimens (n = 14) were scanned on a 3T MRI scanner using our newly-developed sequence. It is based on T2*-weighted imaging (TR, 12 ms; TE for opposed-phase imaging, 6.1 ms, for in-phase imaging, 7.3 ms; flip angle, 40°). The specimens were also scanned on a 320 detector-row CT scanner. Four radiologists visually graded and compared the visibility of the bone shape of eight regions on MRI- and CT-scans using a 5-point grading system. RESULTS: The diagnostic ability of MRI with respect to the 5th metacarpals, femur, fibula, and pelvis was superior to CT (all, P < 0.050); there was no significant difference in the evaluation results of observers with respect to the cervical and lumbar spine, and the 5th metatarsal (0.058 ≤ P ≤ 1.000). However, the diagnostic ability of MRI was significantly inferior to CT for the assessment of the bone shape of the thoracic spine (observers A and C: P = 0.002, observers B and D: P = 0.001). CONCLUSION: The MRI method we developed represents a potential alternative to CT imaging for the evaluation of the fetal bone structure.

Simple modification of arm position improves B1+ and signal homogeneity in the thoracolumbar spine at 3T.

PURPOSE: To evaluate the homogeneity of the radiofrequency magnetic field (B1+ ) and signal intensity using different arm positions during 3T thoracolumbar spinal imaging. MATERIALS AND METHODS: Twenty volunteers were scanned with a four-channel radiofrequency (RF) transmit coil at 3T, with arms on the bed (conventional), arms elevated by 100 mm (arm lift), or with the arms-up position (elevated arm). Axial B1+ maps and sagittal T1 -weighted image (T1 WI)-performed RF shimming were obtained for each arm position. The mean and standard deviation (SD) of the flip angle (FA) at the center of the vertebra on each B1+ map, and contrast noise ratios (CNRs) between the spinal cord and cerebrospinal fluid of sagittal T1 WI, were calculated and compared among the different arm positions. RESULTS: Mean FA values (degrees) for the arm lift and elevated arm positions were significantly larger than for the conventional position (P < 0.001 for both) at the twelfth thoracic vertebra (Th12). FA SD values for the arm lift and elevated arm position were significantly smaller than for the conventional position (P < 0.001 for both) at Th12. CNR for the arm lift and elevated arm position were significantly higher than for the conventional position (P = 0.007 and 0.002, respectively). The mean and SD of the FA and the CNR did not differ significantly for the arm lift and elevated arm positions (P = 0.591, 0.958, and 0.927, respectively). CONCLUSION: Inhomogeneities of B1+ and signal intensities were improved by simply changing the arm position in 3T thoracolumbar spinal imaging. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:123-130.

[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.

Systemic oxidative stress is associated with lower aerobic capacity and impaired skeletal muscle energy metabolism in patients with metabolic syndrome.

OBJECTIVE: Systemic oxidative stress is associated with insulin resistance and obesity. We tested the hypothesis that systemic oxidative stress is linked to lower aerobic capacity and skeletal muscle dysfunction in metabolic syndrome (MetS). RESEARCH DESIGN AND METHODS: The incremental exercise testing with cycle ergometer was performed in 14 male patients with MetS and 13 age-, sex-, and activity-matched healthy subjects. Systemic lipid peroxidation was assessed by serum thiobarbituric acid reactive substances (TBARS), and systemic antioxidant defense capacity was assessed by serum total thiols and enzymatic activity of superoxide dismutase (SOD). To assess skeletal muscle energy metabolism, we measured high-energy phosphates in the calf muscle during plantar flexion exercise and intramyocellular lipid (IMCL) in the resting leg muscle, using (31)P- and (1)proton-magnetic resonance spectroscopy, respectively. RESULTS: Serum TBARS were elevated (12.4 ± 7.1 vs. 3.7 ± 1.1 µmol/L; P < 0.01), and serum total thiols and SOD activity were decreased (290.8 ± 51.2 vs. 398.7 ± 105.2 µmol/L, P < 0.01; and 22.2 ± 8.4 vs. 31.5 ± 8.5 units/L, P < 0.05, respectively) in patients with MetS compared with healthy subjects. Peak VO2 and anaerobic threshold normalized to body weight were significantly lower in MetS patients by 25 and 31%, respectively, and inversely correlated with serum TBARS (r = -0.49 and r = -0.50, respectively). Moreover, muscle phosphocreatine loss during exercise was 1.4-fold greater in patients with MetS (P < 0.05), and IMCL content was 2.9-fold higher in patients with MetS (P < 0.01), indicating impaired skeletal muscle energy metabolism, and these indices positively correlated with serum TBARS (r = 0.45 and r = 0.63, respectively). CONCLUSIONS: Systemic oxidative stress was associated with lower aerobic capacity and impaired skeletal muscle energy metabolism in patients with MetS.

Bilateral cortical hyperactivity detected by fMRI associates with improved motor function following intravenous infusion of mesenchymal stem cells in a rat stroke model.

Intravenous transplantation of mesenchymal stem cells (MSCs) derived from bone marrow ameliorates functional deficits in rat cerebral infarction models. In this study, MSCs were intravenously administered 6h after right middle cerebral artery occlusion (MCAO) induction in rat. Functional MRI (fMRI) during electrical stimulation of the left forepaw and behavioral testing (treadmill stress test) were carried out at day 1, 4, 7, 14, 21, 28 and 42 following MCAO. In medium infused group (n=20) electrical stimulation of the left forepaw elicited a unilateral (right cortex) activated signal detected by fMRI in the infarcted somatosensory cortex. In the MSC infused animals two fMRI patterns were observed: unilateral (n=17) and bilateral (n=19) activation of sensorimotor cortex. In the MSC group both unilateral and bilateral cortical activated animals displayed significantly improved motor function compared to the medium infused group. However, the bilateral activated pattern in the MSC group showed the greatest functional recovery. Lesion volume as calculated from high intensity signals using T2WI was less in the MSC groups as compared to the medium group, but the lesion volume for the unilateral and bilateral signals in the MSC group was the same. These results suggest that the presence of a bilateral signal in sensorimotor cortex as detected by fMRI was more predictive of improved functional outcome than lesion volume alone.

[Study of radiation dose to the eye lens by multi-detector row computed tomography of the temporal bone].

The exposure of the eye lens caused by multi-detector row computed tomography (MDCT) of the temporal bone is a serious problem. Our aim was to evaluate the radiation dose to the eye lens by different scan baselines (orbitomeatal line; OML, acanthiomeatal line; AML) and examine the difference of the depiction of the temporal bone structures. Measurement of the exposure to the eye lens was performed by means of MDCT of the temporal bone with a radio-photoluminescence glass dosimeter using a rand phantom. Moreover, we studied only one volunteer (58-year-old male) who had no symptom and was not suspected of having any ear abnormalities with a two scan baseline. Visualization of the major anatomical structures of the temporal bone (the tympanic portion of the facial nerve canal, the body of the incus, stapes superstructures, vestibule etc.) was performed on the volunteer. The average absorbed dose was 6.42 mGy by the OML and 1.59 mGy by the AML, respectively. With regard to visualization of the temporal bone structures, all structures were of equal quality with the two scan baseline. With the AML line, the radiation dose to the eye lens was reduced to 75%. Therefore, the authors recommended an AML for use for MDCT of the temporal bone. In clinical practice, the optimization of scanning factor (kVp, mAs etc.) and the use of the radio-protection should be implemented for radiation dose reduction of the eye lens by MDCT of the temporal bone.

Therapeutic benefits of human mesenchymal stem cells derived from bone marrow after global cerebral ischemia.

Although intravenous delivery of mesenchymal stem cells (MSCs) prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat middle cerebral artery occlusion models, there are few reports of MSC treatment in global cerebral ischemia. We utilized a global cerebral ischemia model induced by arresting the heart with a combination of hypovolemia and intracardiac injections of a cold potassium chloride solution in order to study the potential therapeutic benefits of human mesenchymal stem cells (hMSCs) on global cerebral ischemia. hMSCs were intravenously injected into the rats 3 h after resuscitation from cardiac arrest. The effects on structural and functional outcome of hMSC were assessed at 5 h and 1, 3, and 7 days using magnetic resonance spectroscopy (MRS), histology, and cognitive functional analysis. Intravenous delivery of hMSCs reduced the Lac/Cr ratios, nuclear DNA fragmentation, neuronal loss, and elicited functional improvement compared with the control sham group. Enzyme-linked immunosorbent assay (ELISA) of the hippocampus revealed an increase in BDNF in hMSC-treated group. These data suggest that intravenous delivery of hMSC may have a therapeutic effect in global cerebral ischemia.

Transient oculomotor palsy correlated with nerve enhancement on MRI in chronic inflammatory demyelinating polyneuropathy.

A 40-year-old woman was admitted to our hospital because of double vision combined with left ptosis. Although at 25 years of age she had already been diagnosed with limb weakness associated with chronic inflammatory demyelinating polyneuropathy (CIDP), she had never experienced double vision until her latest condition. Neurological examination revealed left oculomotor palsy without other cranial nerve involvement. Serial magnetic resonance imaging (MRI) studies demonstrated a temporal correlation between clinical severity of oculomotor palsy and segmental enhancement of the oculomotor nerve. Gadolinium enhancement on MRI may be a significant finding indicating relapse of oculomotor involvement of CIDP.

Susceptibility-weighted magnetic resonance imaging for the detection of cerebral microhemorrhage in patients with traumatic brain injury.

The sensitivity of susceptibility-weighted magnetic resonance (MR) imaging was compared with conventional MR sequences, including T(2)*-weighted imaging, and computed tomography for the detection of cerebral hemorrhages in 15 patients with head injury. Susceptibility-weighted imaging detected a mean of 76+/-52 (total 1132) hypointense spotty lesions, compared to a mean of 21+/-19 (total 316) detected by T(2)*-weighted imaging (p<0.0001, paired t-test). Susceptibility-weighted imaging is extremely sensitive for the visualization and detection of microhemorrhages.

Therapeutic benefits of angiogenetic gene-modified human mesenchymal stem cells after cerebral ischemia.

Intravenous transplantation of human mesenchymal stem cells (hMSCs) expanded from adult bone marrow ameliorates functional deficits in rat cerebral infarction models. Several hypotheses to account for the therapeutic mechanisms have been suggested, but angiogenesis is thought to be of critical importance. Recently, we have reported the therapeutic benefits of hMSCs which have been transfected with the angiopoietin-1 gene in a rat permanent middle cerebral artery occlusion (MCAO) model. To potentially enhance the therapeutic effects of angiopoietin-1 gene-modified hMSC (Ang-hMSC), we transfected hMSCs with the angiopoietin-1 gene and the VEGF gene, and investigated whether the combination of Ang-1 and VEGF gene-modified hMSCs (Ang-VEGF-hMSC) contribute to functional recovery in a rat MCAO model. We induced MCAO using intraluminal vascular occlusion, and hMSCs, Ang-hMSCs, VEGF-hMSCs or Ang-VEGF-hMSCs were intravenously infused 6 h later. MRI and behavioral analyses revealed that rats receiving Ang-VEGF-hMSCs showed the greatest structural-functional recovery as compared to the other groups. These results suggest that intravenous administration of hMSCs transfected with the angiopoietin-1 and VEGF gene using a fiber-mutant adenovirus vector may represent a new strategy for the treatment of ischemia.

Optimization of a therapeutic protocol for intravenous injection of human mesenchymal stem cells after cerebral ischemia in adult rats.

The systemic injection of human mesenchymal stem cells (hMSCs) prepared from adult bone marrow has therapeutic benefits after cerebral artery occlusion in rats, and may have multiple therapeutic effects at various sites and times within the lesion as the cells respond to a particular pathological microenvironment. However, the comparative therapeutic benefits of multiple injections of hMSCs at different time points after cerebral artery occlusion in rats remain unclear. In this study, we induced middle cerebral artery occlusion (MCAO) in rats using intra-luminal vascular occlusion, and infused hMSCs intravenously at a single 6 h time point (low and high cell doses) and various multiple time points after MCAO. From MRI analyses lesion volume was reduced in all hMSC cell injection groups as compared to serum alone injections. However, the greatest therapeutic benefit was achieved following a single high cell dose injection at 6 h post-MCAO, rather than multiple lower cell infusions over multiple time points. Three-dimensional analysis of capillary vessels in the lesion indicated that the capillary volume was equally increased in all of the cell-injected groups. Thus, differences in functional outcome in the hMSC transplantation subgroups are not likely the result of differences in angiogenesis, but rather from differences in neuroprotective effects.