Perfusion deficits in patients with mild traumatic brain injury characterized by dynamic susceptibility contrast MRI

Perfusion deficits in patients with mild traumatic brain injury (TBI) from a military population were characterized by dynamic susceptibility contrast perfusion imaging. Relative cerebral blood flow (rCBF) was calculated by a model‐independent deconvolution approach from the tracer concentration curves following a bolus injection of gadolinium diethylenetriaminepentaacetate (Gd‐DTPA) using both manually and automatically selected arterial input functions (AIFs). Linear regression analysis of the mean values of rCBF from selected regions of interest showed a very good agreement between the two approaches, with a regression coefficient of R = 0.88 and a slope of 0.88. The Bland–Altman plot also illustrated the good agreement between the two approaches, with a mean difference of 0.6 ± 12.4 mL/100 g/min. Voxelwise analysis of rCBF maps from both approaches demonstrated multiple clusters of decreased perfusion (p < 0.01) in the cerebellum, cuneus, cingulate and temporal gyrus in the group with mild TBI relative to the controls. MRI perfusion deficits in the cerebellum and anterior cingulate also correlated (p < 0.01) with neurocognitive results, including the mean reaction time in the Automated Neuropsychological Assessment Metrics and commission error and detection T‐scores in the Continuous Performance Test, as well as neurobehavioral scores in the Post‐traumatic Stress Disorder Checklist–Civilian Version. In conclusion, rCBF calculated using AIFs selected from an automated approach demonstrated a good agreement with the corresponding results using manually selected AIFs. Group analysis of patients with mild TBI from a military population demonstrated scattered perfusion deficits, which showed significant correlations with measures of verbal memory, speed of reaction time and self‐report of stress symptoms. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.     

Pulmonary perfusion quantification with flow‐sensitive inversion recovery (FAIR) UTE MRI in small animal imaging

Blood perfusion in lung parenchyma is an important property for assessing lung function. In small animals, its quantitation is limited even with radioactive isotopes or dynamic contrast‐enhanced MRI techniques. In this study, the feasibility flow‐sensitive alternating inversion recovery (FAIR) for the quantification of blood flow in lung parenchyma in free breathing rats at 7 T has been investigated. In order to obtain sufficient signal from the short T₂* lung parenchyma, a 2D ultra‐short echo time (UTE) Look‐Locker read‐out has been implemented. Acquisitions were segmented to maintain acquisition time within an acceptable range. A method to perform retrospective respiratory gating (DC‐SG) has been applied to investigate the impact of respiratory movement. Reproducibilities within and between sessions were estimated, and the ability of FAIR‐UTE to identify the decrease of lung perfusion under hyperoxic conditions was tested. The implemented technique allowed for the visualization of lung parenchyma with excellent SNR and no respiratory artifact even in ungated acquisitions. Lung parenchyma perfusion was obtained as 32.54 ± 2.26 mL/g/min in the left lung, and 34.09 ± 2.75 mL/g/min in the right lung. Application of retrospective gating significantly but minimally changes the perfusion values, implying that respiratory gating may not be necessary with this center‐our acquisition method. A decrease of 10% in lung perfusion was found between normoxic and hyperoxic conditions, proving the feasibility of the FAIR‐UTE approach to quantify lung perfusion changes.     

Comparison between coated vs. uncoated suture middle cerebral artery occlusion in the rat as assessed by perfusion/diffusion weighted imaging

Differences among models in the temporal evolution of ischemia after middle cerebral artery occlusion (MCAO) in rats may considerably influence the results of experimental treatment studies. Using diffusion and perfusion imaging, we compared the spatiotemporal evolution of ischemia in Sprague-Dawley rats after permanent MCAO (pMCAO) with different types of sutures. Male Sprague-Dawley rats were randomly assigned to pMCAO produced with either 4-0 silicone coated (n=8), or 3-0 uncoated monofilaments (n=8). Serial determination of quantitative cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) maps were performed up to 3 h after pMCAO. Lesion volumes were calculated by using previously validated thresholds and correlated with infarct volume corrected for edema defined by 2,3,5-triphenyltetrazolium chloride (TTC) staining at 24 h after MCAO. The ADC/CBF-defined mismatch volume in the 4-0 coated suture model was present significantly longer (up to 120 min) compared to the uncoated 3-0 suture model (30 min). The TTC-derived infarct volume was significantly larger in the coated model (290.3+/-32.8 mm(3)) relative to the uncoated model (252.3+/-34.6 mm(3)). This study demonstrates that the type of suture may significantly influence the spatiotemporal evolution of the ADC/CBF-mismatch as well as the final infarct volume. These inter-model variations must be taken into account when assessing new therapeutic approaches on ischemic lesion evolution in the rat MCAO model.     

A comparison of arterial spin labeling perfusion MRI and DCE‐MRI in human prostate cancer

Perfusion MRI has the potential to provide pathophysiological biomarkers for the evaluating, staging and therapy monitoring of prostate cancer. The objective of this study was to explore the feasibility of noninvasive arterial spin labeling (ASL) to detect prostate cancer in the peripheral zone and to investigate the correlation between the blood flow (BF) measured by ASL and the pharmacokinetic parameters K^trans (forward volume transfer constant), k_ep (reverse reflux rate constant between extracellular space and plasma) and v_e (the fractional volume of extracellular space per unit volume of tissue) measured by dynamic contrast‐enhanced (DCE) MRI in patients with prostate cancer. Forty‐three consecutive patients (ages ranging from 49 to 86 years, with a median age of 74 years) with pathologically confirmed prostate cancer were recruited. An ASL scan with four different inversion times (TI = 1000, 1200, 1400 and 1600 ms) and a DCE‐MRI scan were performed on a clinical 3.0 T GE scanner. BF, K^trans, k_ep and v_e maps were calculated. In order to determine whether the BF values in the cancerous area were statistically different from those in the noncancerous area, an independent t‐test was performed. Spearman's bivariate correlation was used to assess the relationship between BF and the pharmacokinetic parameters K^trans, k_ep and v_e. The mean BF values in the cancerous areas (97.1 ± 30.7, 114.7 ± 28.7, 102.3 ± 22.5, 91.2 ± 24.2 ml/100 g/min, respectively, for TI = 1000, 1200, 1400, 1600 ms) were significantly higher (p < 0.01 for all cases) than those in the noncancerous regions (35.8 ± 12.5, 42.2 ± 13.7, 53.5 ± 19.1, 48.5 ± 13.5 ml/100 g/min, respectively). Significant positive correlations (p < 0.01 for all cases) between BF and the pharmacokinetic parameters K^trans, k_ep and v_e were also observed for all four TI values (r = 0.671, 0.407, 0.666 for TI = 1000 ms; 0.713, 0.424, 0.698 for TI = 1200 ms; 0.604, 0.402, 0.595 for TI = 1400 ms; 0.605, 0.422, 0.548 for TI = 1600 ms). It can be seen that the quantitative ASL measurements show significant differences between cancerous and benign tissues, and exhibit strong to moderate correlations with the parameters obtained using DCE‐MRI. These results show the promise of ASL as a noninvasive alternative to DCE‐MRI. Copyright © 2014 John Wiley & Sons, Ltd.     

L-丝氨酸对永久性大脑中动脉栓塞大鼠的神经保护作用

目的: 研究L-丝氨酸对大鼠永久性脑梗死的神经保护作用、治疗剂量及有效治疗时间窗,并探讨相关作用机制。方法: 制作大鼠永久性大脑中动脉栓塞(pMCAO)模型,腹腔注射L-丝氨酸,通过神经行为学评分、脑梗死体积测定和尼氏染色法,观察L-丝氨酸的治疗剂量效应(56 mg/kg、168 mg/kg和504 mg/kg治疗组)和治疗时间窗(1 h、3 h、6 h、12 h和24 h治疗组);并测定丝氨酸消旋酶抑制剂对L-丝氨酸疗效的影响。利用激光多普勒血流监测仪观察缺血区血供及L-丝氨酸对缺血区局部脑血流量的影响。结果: 与pMCAO组相比,L-丝氨酸于pMCAO后3 h使用,168 mg/kg和504 mg/kg两个剂量都能较好地降低神经行为学评分,减少脑梗死体积,抑制海马CA1区神经细胞的丢失。在治疗时间窗的研究中,L-丝氨酸在pMCAO后6 h内治疗具有明显的神经保护作用,12 h及以后使用,神经保护作用不明显。丝氨酸消旋酶抑制剂不改变L-丝氨酸的疗效。脑缺血30 min时注射L-丝氨酸可明显增加缺血区局部脑血流量,并且这一作用不受甘氨酸受体阻断剂士的宁的影响。结论: L-丝氨酸对永久性脑梗死具有神经保护作用,其机制可能部分与增加缺血区皮质的血供有关。     

Comparative analysis of arterial spin labeling and dynamic susceptibility contrast perfusion imaging for quantitative perfusion measurements of brain tumors

We comparatively analyzed the difference between three-dimensional arterial spin labeling (3D-ASL) and the conventional dynamic susceptibility contrast (DSC) perfusion imaging in the setting of assessing brain tumor perfusion in 28 patients with proved brain tumors. All patients were scheduled with standard MRI, 3D-ASL and DSC scannings on a GE DISCOVERY MR 750 system. Maximal relative tumor perfusion was obtained based on the region of interest (ROI) method. A close correlation between 3D-ASL and DSC perfusion imaging was noted as manifested by the absence of significant differences between ASL nTBF and DSC nTBF when normalized to M (mirror region) and GM (contralateral gray matter). However, ASL nTBF was found to be highly correlated with DSC nTBF and DSC nTBV when normalized to M, GM and WM (contralateral normal white matter). Together, our data support that 3D-ASL possesses the potential to be a noninvasive alternate for DSC-MRI in assessing brain tumor perfusion in the setting of treatment prognosis and metastasis, particularly for those patients with renal failure and patients required for collection of follow up information.     

Relationship between diffusion parameters derived from intravoxel incoherent motion MRI and perfusion measured by dynamic contrast‐enhanced MRI of soft tissue tumors

Our aim was to evaluate the link between diffusion parameters measured by intravoxel incoherent motion (IVIM) diffusion‐weighted imaging (DWI) and the perfusion metrics obtained with dynamic contrast‐enhanced (DCE) MRI in soft tissue tumors (STTs). Twenty‐eight patients affected by histopathologically confirmed STT were included in a prospective study. All patients underwent both DCE MRI and IVIM DWI. The perfusion fraction f, diffusion coefficient D and perfusion‐related diffusion coefficient D* were estimated using a bi‐exponential function to fit the DWI data. DCE MRI was acquired with a temporal resolution of 3–5 s. Maps of the initial area under the gadolinium concentration curve (IAUGC), time to peak (TTP) and maximum slope of increase (MSI) were derived using commercial software. The relationships between the DCE MRI and IVIM DWI measurements were assessed by Spearman's test. To exclude false positive results under multiple testing, the false discovery rate (FDR) procedure was applied. The Mann–Whitney test was used to evaluate the differences between all variables in patients with non‐myxoid and myxoid STT. No significant relationship was found between IVIM parameters and any DCE MRI parameters. Higher f and D*f values were found in non‐myxoid tumors compared with myxoid tumors (p = 0.004 and p = 0.003, respectively). MSI was significantly higher in non‐myxoid tumors than in myxoid tumors (p = 0.029). From the visual assessments of single clinical cases, both f and D*f maps were in satisfactory agreement with DCE maps in the extreme cases of an avascular mass and a highly vascularized mass, whereas, for tumors with slight vascularity or with a highly heterogeneous perfusion pattern, this association was not straightforward. Although IVIM DWI was demonstrated to be feasible in STT, our data did not support evident relationships between perfusion‐related IVIM parameters and perfusion measured by DCE MRI. Copyright © 2015 John Wiley & Sons, Ltd.     

Identifying systematic errors in quantitative dynamic-susceptibility contrast perfusion imaging by high-resolution multi-echo parallel EPI

Several obstacles usually confound a straightforward perfusion analysis using dynamic-susceptibility contrast-based magnetic resonance imaging (DSC-MRI). In this work, it became possible to eliminate some of these sources of error by combining a multiple gradient-echo technique with parallel imaging (PI): first, the large dynamic range of tracer concentrations could be covered satisfactorily with multiple echo times (TE) which would otherwise result in overestimation of image magnitude in the presence of noise. Second, any bias from T(1) relaxation could be avoided by fitting to the signal magnitude of multiple TEs. Finally, with PI, a good tradeoff can be achieved between number of echoes, brain coverage, temporal resolution and spatial resolution. The latter reduces partial voluming, which could distort calculation of the arterial input function. Having ruled out these sources of error, a 4-fold overestimation of cerebral blood volume and flow remained, which was most likely due to the completely different relaxation mechanisms that are effective in arterial voxels compared with tissue. Hence, the uniform tissue-independent linear dependency of relaxation rate upon tracer concentration, which is usually assumed, must be questioned. Therefore, DSC-MRI requires knowledge of the exact dependency of transverse relaxation rate upon tracer concentration in order to calculate truly quantitative perfusion maps.     

Nylon filament coated with paraffin for intraluminal permanent middle cerebral artery occlusion in rats

A variety of intraluminal nylon filament has been used in rat middle cerebral artery occlusion (MCAO) models. However the lesion extent and its reproducibility vary among laboratories. The properties of nylon filament play a part of reasons for these variations. In the present study, we used paraffin-coated nylon filament for rat MCAO model, tested the effects and advanced improvement for making the rat MCAO. Forty male Sprague-Dawley (SD) rats were randomized into two groups, MCAO with traditional uncoated nylon filament (uMCAO) and MCAO with paraffin-coated nylon filament (cMCAO), three rats as normal group and sham group respectively. Assessment included mortality rates, model success rates, neurological deficit evaluation, and infarct volume. The study showed two rats died in uMCAO group, no rat died in cMCAO group within the 12 h. The model success rate of uMCAO was 100%, while the uMCAO group was 55% (n = 20, two died within 12 h, seven rats were excluded as the brain slices showed no TTC staining due to subarachanoid hemorrhage). Neurological evaluation demonstrated group cMCAO had more worse neurological outcomes than group uMCAO, and the difference was statistically signification (p < 0.05). TTC staining cMCAO group had significantly larger infarct volumes than uMCAO group, and also showed statistically significant difference (p < 0.05). The result demonstrated that the paraffin-coated nylon filament intraluminal occlusion provide better occlusion of middle cerebral artery than the uncoated nylon filament, improve the consistent of model, and raise the success rate to reduce the number of experimental animals. These positive results are much encouraging and interesting.     

Nylon filament coated with paraffin for intraluminal permanent middle cerebral artery occlusion in rats

Decreased dopamine (DA) release in the hippocampus may be caused by dysfunctional mastication, although the mechanisms involved remain unclear. The present study examined the effects of soft- and hard-food diets on oxidative stress in the brain, and the relationship between these effects and hippocampal DA levels. The present study showed that DA release in the hippocampus was decreased in rats fed a soft-food diet. Electron spin resonance studies using the nitroxyl spin probe 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl directly demonstrated a high level of oxidative stress in the rat brain due to soft-food diet feeding. In addition, we confirmed that DA directly react with reactive oxygen species such as hydroxyl radical and superoxide. These observations suggest that soft-food diet feeding enhances oxidative stress, which leads to oxidation and a decrease in the release of DA in the hippocampus of rats.     

Dynamic contrast-enhanced MRI of muscle perfusion combined with MR angiography of collateral artery growth in a femoral artery ligation model

To assess the use of MRI for evaluating changes in muscle blood flow and number of collateral arteries, serial dynamic contrast-enhanced MRI (DCE-MRI) was combined with high-spatial-resolution contrast-enhanced MR angiography (MRA) in a peripheral ischemia model.The combined MRI (DCE-MRI and MRA) protocol was performed serially in 15 male rabbits at 2 h (day 0(+)), 7 days, and 21 days after femoral artery ligation. In the anterior tibial and soleus muscle, changes in resting muscle blood flow determined as the endothelial transfer coefficient (K(trans)) and arterial inflow delay from DCE-MRI and changes in the number of sub-millimeter sized collateral arteries as scored with MRA were measured. Directly after ligation, K(trans) in the anterior tibial muscle was reduced to 23% of that in the control limb, then recovered to 81% on day 7, and to 85 % on day 21. K(trans) in the soleus muscle recovered from a reduction to 63% on day 0(+), to 85% on day 7, and to 90% on day 21. The number of collaterals around the ligated femoral artery increased from 1.1 on day 0(+) to 4.2 on day 7, and 6.0 on day 21 in the ligated limb only. Combined DCE-MRI and MRA allows non-invasive serial monitoring of changes in muscle blood flow and growth of sub-millimeter sized collateral arteries in a rabbit femoral artery ligation model.     

MR fingerprinting ASL: Sequence characterization and comparison with dynamic susceptibility contrast (DSC) MRI

MR Fingerprinting (MRF)‐based Arterial‐Spin‐Labeling (ASL) has the potential to measure multiple parameters such as cerebral blood flow (CBF), bolus arrival time (BAT), and tissue T₁ in a single scan. However, the previous reports have only demonstrated a proof‐of‐principle of the technique but have not examined the performance of the sequence in the context of key imaging parameters. Furthermore, there has not been a study to directly compare the technique to clinically used perfusion method of dynamic‐susceptibility‐contrast (DSC) MRI. The present report consists of two studies. In the first study (N = 8), we examined the dependence of MRF‐ASL sequence on TR time pattern. Ten different TR patterns with a range of temporal characteristics were examined by both simulations and experiments. The results revealed that there was a significance dependence of the sequence performance on TR pattern (p < 0.001), although there was not a single pattern that provided dramatically improvements. Among the TR patterns tested, a sinusoidal pattern with a period of 125 TRs provided an overall best estimation in terms of spatial consistency. These experimental observations were consistent with those of numerical simulations. In the second study (N = 8), we compared MRF‐ASL results with those of DSC MRI. It was found that MRF‐ASL and DSC MRI provided highly comparable maps of cerebral blood flow (CBF) and bolus‐arrival‐time (BAT), with spatial correlation coefficients of 0.79 and 0.91, respectively. However, in terms of quantitative values, BAT obtained with MRF‐ASL was considerably lower than that from DSC (p < 0.001), presumably because of the differences in tracer characteristics in terms of diffusible versus intravascular tracers. Test–retest assessment of MRF‐ASL MRI revealed that the spatial correlations of parametric maps were 0.997, 0.962, 0.746 and 0.863 for B₁⁺, T₁, CBF, and BAT, respectively. MRF‐ASL is a promising technique for assessing multiple perfusion parameters simultaneously without contrast agent.     

Non‐invasive and quantitative evaluation of peripheral vascular resistances in rats by combined NMR measurements of perfusion and blood pressure using ASL and dynamic angiography

The in vivo determination of peripheral vascular resistances (VR) is crucial for the assessment of arteriolar function. It requires simultaneous determination of organ perfusion (F) and arterial blood pressure (BP). A fully non‐invasive method was developed to measure systolic and diastolic BP in the caudal artery of rats based on dynamic NMR angiography. A good agreement was found between the NMR approach and the gold standard techniques (linear regression slope = 0.98, R² = 0.96). This method and the ASL‐MRI measurement of skeletal muscle perfusion were combined into one single NMR experiment to quantitatively evaluate the local vascular resistances in the calf muscle of anaesthetized rats, in vivo and non‐invasively 1) at rest: VR = 7.0 ± 1.0 mmHg·min 100 g·ml^?1, F = 13 ± 3 ml min^?1.100 g^?1 and mean BP (MBP) = 88 ± 10 mmHg; 2) under vasodilator challenge (milrinone): VR = 3.7 ± 1.1 mmHg min.100 g ml^?1, F = 21 ± 4 ml min^?1.100 g^?1 and MBP = 75 ± 14 mmHg; 3) under vasopressor challenge (norepinephrine): VR = 9.8 ± 1.2 mmHg min 100 g ml^?1, F = 14 ± 3 ml min^?1.100 g^?1 and MBP = 137 ± 2 mmHg. Copyright © 2009 John Wiley & Sons, Ltd.     

The capability of detecting small vessels beyond the conventional MRI sensitivity using iron‐based contrast agent enhanced susceptibility weighted imaging

Imaging brain microvasculature is important in cerebrovascular diseases. However, there is still a lack of non‐invasive, non‐radiation, and whole‐body imaging techniques to investigate them. The aim of this study is to develop an ultra‐small superparamagnetic iron oxide (USPIO) enhanced susceptibility weighted imaging (SWI) method for imaging micro‐vasculature in both animal (~10 μm in rat) and human brain. We hypothesized that the USPIO‐SWI technique could improve the detection sensitivity of the diameter of small subpixel vessels 10‐fold compared with conventional MRI methods. Computer simulations were first performed with a double‐cylinder digital model to investigate the theoretical basis for this hypothesis. The theoretical results were verified using in vitro phantom studies and in vivo rat MRI studies (n = 6) with corresponding ex vivo histological examinations. Additionally, in vivo human studies (n = 3) were carried out to demonstrate the translational power of the USPIO‐SWI method. By directly comparing the small vessel diameters of an in vivo rat using USPIO‐SWI with the small vessel diameters of the corresponding histological slide using laser scanning confocal microscopy, 13.3‐fold and 19.9‐fold increases in SWI apparent diameter were obtained with 5.6 mg Fe/kg and 16.8 mg Fe/kg ferumoxytol, respectively. The USPIO‐SWI method exhibited its excellent ability to detect small vessels down to about 10 μm diameter in rat brain. The in vivo human study unveiled hidden arterioles and venules and demonstrated its potential in clinical practice. Theoretical modeling simulations and in vitro phantom studies also confirmed a more than 10‐fold increase in the USPIO‐SWI apparent diameter compared with the actual small vessel diameter size. It is feasible to use SWI blooming effects induced by USPIO to detect small vessels (down to 10 μm in diameter for rat brain), well beyond the spatial resolution limit of conventional MRI methods. The USPIO‐SWI method demonstrates higher potential in cerebrovascular disease investigations.     

MRI of retinal and choroidal blood flow with laminar resolution

The retina is nourished by two distinct circulations: the retinal vessels within the inner retina and the choroidal vessels behind the neural retina. The outer nuclear layer and the inner and outer segments of the photoreceptors in between are avascular. The aim of this study was to determine whether arterial spin labeling MRI could provide sufficient resolution to differentiate between quantitative retinal blood flow (rBF) and choroidal blood flow (chBF), and whether this technique is sufficiently sensitive to detect vascular‐specific blood flow (BF) changes modulated by anesthetics. Arterial spin labeling MRI was performed at 42 × 42 × 400 µm³ in the mouse retina at 7 T, and was used to investigate the effects of isoflurane and ketamine/xylazine anesthesia on rBF and chBF. MRI yielded unambiguous differentiation of rBF, chBF and the avascular layer in between. Under isoflurane, chBF was 7.7 ± 2.1 mL/g/min and rBF was 1.3 ± 0.44 mL/g/min (mean ± SD, n = 7, p < 0.01). Under ketamine/xylazine anesthesia in the same animals, chBF was 4.3 ± 1.9 mL/g/min and rBF was 0.88 ± 0.22 mL/g/min (p < 0.01). Under ketamine/xylazine anesthesia, rBF was lower by 29% (P < 0.01) and chBF by 42% (P < 0.01) relative to isoflurane. This study demonstrates, for the first time, the quantitative imaging of rBF and chBF in vivo, providing a new method to study basal values and alterations of rBF and chBF. Copyright © 2010 John Wiley & Sons, Ltd.     

Structural MRI of carotid artery atherosclerotic lesion burden and characterization of hemispheric cerebral blood flow before and after carotid endarterectomy

Collateral circulation plays a major role in maintaining cerebral blood flow (CBF) in patients with internal carotid artery (ICA) stenosis. CBF can remain normal despite severe ICA stenosis, making the benefit of carotid endarterectomy (CEA) or stenting difficult to assess. Before and after surgery, we assessed CBF supplied through the ipsilateral (stenotic) or contralateral ICA individually with a novel hemisphere-selective arterial spin-labeling (ASL) perfusion MR technique. We further explored the relationship between CBF and ICA obstruction ratio (OR) acquired with a multislice black-blood imaging sequence. For patients with unilateral ICA stenosis (n = 19), conventional bilateral labeling did not reveal interhemispheric differences. With unilateral labeling, CBF in the middle cerebral artery (MCA) territory on the surgical side from the ipsilateral supply (53.7 +/- 3.3 ml/100 g/min) was lower than CBF in the contralateral MCA territory from the contralateral supply (58.5 +/- 2.7 ml/100 g/min), although not statistically significant (p = 0.09). The ipsilateral MCA territory received significant (p = 0.02) contralateral supply (7.0 +/- 2.7 ml/100 g/min), while ipsilateral supply to the contralateral side was not reciprocated. After surgery (n = 11), ipsilateral supply to the MCA territory increased from 57.3 +/- 5.7 to 67.3 +/- 5.4 ml/100 g/min (p = 0.03), and contralateral supply to the ipsilateral MCA territory decreased. The best predictor of increased CBF on the side of surgery was normalized presurgical ipsilateral supply (r(2) = 0.62, p = 0.004). OR was less predictive of change, although the change in normalized contralateral supply was negatively correlated with OR(excess) (=OR(ipsilateral) - OR(contralateral)) (r(2) = 0.58, p = 0.006). The results demonstrate the effect of carotid artery stenosis on blood supply to the cerebral hemispheres, as well as the relative role of collateral pathways before surgery and redistribution of blood flow through these pathways after surgery. Unilateral ASL may better predict hemodynamic surgical outcome (measured by improved perfusion) than ICA OR.     

Vessel size index measurements in a rat model of glioma: comparison of the dynamic (Gd) and steady-state (iron-oxide) susceptibility contrast MRI approaches

Vessel size index (VSI), a parameter related to the distribution of vessel diameters, may be estimated using two MRI approaches: (i) dynamic susceptibility contrast (DSC) MRI following the injection of a bolus of Gd‐chelate. This technique is routinely applied in the clinic to assess intracranial tissue perfusion in patients; (ii) steady‐state susceptibility contrast with USPIO contrast agents, which is considered here as the standard method. Such agents are not available for human yet and the steady‐state approach is currently limited to animal studies. The aim is to compare VSI estimates obtained with these two approaches on rats bearing C6 glioma (n = 7). In a first session, VSI was estimated from two consecutive injections of Gd‐Chelate (Gd₁ and Gd₂). In a second session (4 hours later), VSI was estimated using USPIO. Our findings indicate that both approaches yield comparable VSI estimates both in contralateral (VSI{USPIO} = 7.5 ± 2.0 µm, VSI{Gd₁} = 6.5 ± 0.7 µm) and in brain tumour tissues (VSI{USPIO} = 19.4 ± 7.1 µm, VSI{Gd₁} = 16.6 ± 4.5 µm). We also observed that, in the presence of BBB leakage (as it occurs typically in brain tumours), applying a preload of Gd‐chelate improves the VSI estimate with the DSC approach both in contralateral (VSI{Gd₂} = 7.1 ± 0.4 µm) and in brain tumour tissues (VSI{Gd₂} = 18.5 ± 4.3 µm) but is not mandatory. VSI estimates do not appear to be sensitive to T₁ changes related to Gd extravasation. These results suggest that robust VSI estimates may be obtained in patients at 3 T or higher magnetic fields with the DSC approach. Copyright © 2011 John Wiley & Sons, Ltd.     

Ketamine-induced rotational asymmetry in evaluation of motor disturbances in rats with middle cerebral artery occlusion

Intraperitoneal injection of ketamine in subanesthetic doses to Wistar rats with unilateral occlusion of the middle cerebral artery caused ipsilateral rotation (2-10 rpm), which was recorded in an automatic rotameter. The optimal dose of ketamine was 50 mg/kg. The animals were examined in an automatic rotameter for 40 min. Motor asymmetry persisted for no less than 2 months after surgery. According to the neurological test (Menzies scale) motor asymmetry in animals with focal brain ischemia persisted for no more than 30 days. The degree of ketamine-induced motor asymmetry in intact rats was 0.10±0.03 rpm.     

Comparison of administration routes for adipose-derived stem cells in the treatment of middle cerebral artery occlusion in rats

Given that adult adipose tissue is an abundant, accessible and safe source of stem cells, the use of adipose-derived stem cells (ADSCs) provides a promising approach in ischemic stroke. The delivery route, however, for transplantation of ADSCs in clinical application remains controversial regarding the time window, cell type, safety issues, ‘first pass’ effect and therapeutic effect. To determine the optimal administration route in transplantation of ADSCs, we compared the therapeutic effect of the three mainly used administration routes of ADSCs in a middle cerebral artery occlusion (MCAO) rat model. Cells isolated from the adipose tissue of adult rodents were differentiated and characterized in vitro, and further transplanted in vivo by intravenous, intra-arterial or intra-ventricular delivery. The infarct volume, expression of neurotrophic factors and the neurobehavioral improvements were evaluated after the equal dose of BrdU labeled ADSCs transplantation. Our results indicated that the equal dose of ADSCs delivered intravenously were effective in improving the neurological outcome and reducing the infarct volume after ischemic brain injury in long term duration in contrast to intra-arterial and intra-ventricular delivery. At 1–7 days after transplantation, the increased expression levels of BDNF, VEGF, bFGF, Bcl-2, IL-10 and decreased levels of caspase-3 and TNF-α in the intra-ventricular and intra-arterial groups were significant in contrast to the intravenous group. There was no significant difference among the three groups after 7 days. Our findings suggest that compared with the intra-ventricular delivery, intravascular injection allows higher dose injection with fewer invasions and appears to be optimal in application with regard to therapeutic efficacy, safety and feasibility.     

定量磁共振灌注成像用于评价直肠癌的微血管灌注及渗透性

 目的: 采用定量磁共振(MR)灌注成像测定直肠癌的各灌注参数,以探究MR灌注成像在评价肿瘤局部微血管灌注量及渗透性方面的应用价值。方法: 回顾性分析行直肠动态对比增强磁共振(DCE-MRI)扫描的直肠癌患者38例。计算肿瘤和正常肠壁感兴趣区(ROI)灌注参数 的平均值,并对肿瘤与正常肠壁、黏液腺癌与非黏液腺癌、不同分化程度及是否伴淋巴结转移的患者各灌注参数值进行比较分析。结果: 直肠癌的各灌注参数均较正常肠壁高,差异具有统计学意义(P<0.01)。直肠黏液腺癌较非黏液腺癌的K^trans值低(P<0.05)。不同分化程度、伴有或不伴有淋巴结转移直肠癌患者的K^trans、K_ep及V_e差异无统计学意义,伴有淋巴结转移的直肠癌iAUC较不伴者低。结论: 定量MR灌注成像验证了直肠癌较正常肠壁局部微血管灌注及渗透性的改变,并可用于鉴别黏液腺癌与非黏液腺癌的组织学分型,具有一定的诊断应用价值。但是仅根据肿瘤的灌注值来判断肿瘤的分化程度及淋巴结转移尚不可靠。