Xiao-Quan Xu

In Vivo MR Imaging of Intraarterially Delivered Magnetically Labeled Mesenchymal Stem Cells in a Canine Stroke Model

Background This study aimed to evaluate the feasibility of intraarterial (IA) delivery and in vivo MR imaging of superparamagnetic iron oxide (SPIO)-labeled mesenchymal stem cells (MSCs) in a canine stroke model. Methodology MSCs harvested from beagles’ bone marrow were labeled with home-synthesized SPIO. Adult beagle dogs (n = 12) were subjected to left proximal middle cerebral artery (MCA) occlusion by autologous thrombus, followed by two-hour left internal carotid artery (ICA) occlusion with 5 French vertebral catheter. One week later, dogs were classified as three groups before transplantation: group A: complete MCA recanalization, group B: incomplete MCA recanalization, group C: no MCA recanalization. 3×106 labeled-MSCs were delivered through left ICA. Series in vivo MRI images were obtained before cell grafting, one and 24 hours after transplantation and weekly thereafter until four weeks. MRI findings were compared with histological studies at the time point of 24 hours and four weeks. Principal Findings Home-synthesized SPIO was useful to label MSCs without cell viability compromise. MSCs scattered widely in the left cerebral hemisphere in group A, while fewer grafted cells were observed in group B and no cell was detected in group C at one hour after transplantation. A larger infarction on the day of cell transplantation was associated with more grafted cells in the brain. Grafted MSCs could be tracked effectively by MRI within four weeks and were found in peri-infarction area by Prussian blue staining. Conclusion It is feasible of IA MSCs transplantation in a canine stroke model. Both the ipsilateral MCA condition and infarction volume before transplantation may affect the amount of grafted cells in target brain. In vivo MR imaging is useful for tracking IA delivered MSCs after SPIO labeling.

Utility of histogram analysis of ADC maps for differentiating orbital tumors

PURPOSE We aimed to evaluate the role of histogram analysis of apparent diffusion coefficient (ADC) maps for differentiating benign and malignant orbital tumors. METHODS Fifty-two patients with orbital tumors were enrolled from March 2013 to November 2014. Pretreatment diffusion-weighted imaging was performed on a 3T magnetic resonance scanner with b factors of 0 and 800 s/mm2, and the corresponding ADC maps were generated. Whole-tumor regions of interest were drawn on all slices of the ADC maps to obtain histogram parameters, including ADCmean, ADCmedian, standard deviation (SD), skewness, kurtosis, quartile, ADC10, ADC25, ADC75, and ADC90. Histogram parameter differences between benign and malignant orbital tumors were compared. The diagnostic value of each significant parameter in predicting malignant tumors was established. RESULTS Age, ADCmean, ADCmedian, quartile, kurtosis, ADC10, ADC25, ADC75, and ADC90 parameters were significantly different between benign and malignant orbital tumor groups, while gender, location, SD, and skewness were not significantly different. The best diagnostic performance in predicting malignant orbital tumors was achieved at the threshold of ADC10=0.990 (AUC, 0.997; sensitivity, 96.2%; specificity, 100%). CONCLUSION Histogram analysis of ADC maps holds promise for differentiating benign and malignant orbital tumors. ADC10 has the potential to be the most significant parameter for predicting malignant orbital tumors.

A novel embolic stroke model resembling lacunar infarction following proximal middle cerebral artery occlusion in beagle dogs.

It is estimated that lacunar infarcts account for 25% of all ischemic strokes, but its exact etiology is still on debating. The existing controversies include whether the embolisms can indeed cause lacunar stroke in humans or animal models. We hypothesized that lacunar infarction can be induced by the proximal middle cerebral artery (MCA) segmental occlusion involving the orifices of lenticulostriate arteries in animal models, which have abundant distal cerebral collateral anastomosis. Our work here establishes a proximal MCA occlusion model using thrombi (autologous blood clots about 1.7 mm in diameter and 5 mm in length) in 8 beagle dogs, evaluates the progression of ischemic lesions at 30 min interval within 6 h after embolization using the diffusion weighted imaging (DWI), and discusses the potential mechanisms of lacunar infarction. Our results indicate that the left proximal MCAs can be successfully occluded in all dogs using interventional single-thrombus method. The small solitary or multiple ischemic lesions shown in DWI were observed in the deep brain area, with the mean detecting time of 1.21 ± 0.45 h using DWI and diameter of 6.62 ± 0.60mm in 6h-DWI after procedure. In conclusion, our method established an ischemic model which can recapitulate the radiologic and histologic changes in lacunar infarcts, suggesting that emboli can cause lacunar infarcts in animal model.

Benign and malignant orbital lymphoproliferative disorders: Differentiating using multiparametric MRI at 3.0T.

To determine the optimal combination of parameters derived from 3T multiparametric (conventional magnetic resonance imaging [MRI], diffusion‐weighted [DW] and dynamic contrast‐enhanced [DCE]) MRI for differentiating malignant from benign orbital lymphoproliferative disorders (OLPDs).

Use of FLAIR Imaging to Identify Onset Time of Cerebral Ischemia in a Canine Model

After an infarction-inducing procedure, 20 dogs were imaged at 3, 4, 5, 6, and 24 hours with FLAIR and DWI. A mismatch between the 2 sequences (positive DWI and negative FLAIR) was found to reliably predict the time of infarct onset. By 6 hours, 95% of dogs had FLAIR abnormalities and by 24 hours all did. However, at 3 hours only 15% of dogs showed positive FLAIR studies. These results could serve as guidelines to estimate the time of onset of ischemic events. BACKGROUND AND PURPOSE: Stroke is a leading cause of death and disability, and many studies have focused on the evolution of FLAIR imaging in the acute and chronic time window. The purpose of this study was to evaluate the potential efficacy of FLAIR-related techniques in identifying the onset time of cerebral ischemia in a canine embolic stroke model. MATERIALS AND METHODS: An embolic ischemic model was generated through the use of an autologous clot in 20 beagle dogs. Both FLAIR and DWI were performed at 3 hours, 4 hours, 5 hours, 6 hours, and 24 hours after embolization, respectively. Visual “DWI-FLAIR mismatch” was defined as hyperintense signal detected on DWI but not on FLAIR. The relative signal intensity of FLAIR-positive lesions and the degree of DWI-FLAIR mismatch was calculated as relative FLAIR = relative signal intensity of FLAIR positive lesions, mismatch degree = (100−VFLAIR/VDWI) × 100%. RESULTS: The ischemic model was successfully established in all animals. FLAIR-positive lesions were seen in 3, 11, 16, 19, and 20 beagle dogs at 5 time points after embolization, respectively. There was significant correlation between the relative FLAIR, degree of DWI-FLAIR mismatch, and the onset time (relative FLAIR: r = +0.42; 95% CI, 0.20–0.60; mismatch degree: r = −0.85; 95% CI, 0.89–0.78). Receiver operating characteristic curves showed that the degree of DWI-FLAIR mismatch could identify the hyperacute ischemic lesions with a sensitivity range from 1.00–0.76; visual DWI-FLAIR mismatch sensitivity ranged from 0.85–0.39, whereas specificity was 0.83–0.95 versus 0.85–1.00. CONCLUSIONS: The relative FLAIR and DWI-FLAIR mismatch values were useful in predicting the onset time in our canine embolic stroke model. The degree of DWI-FLAIR mismatch proposed in our study could be a good indicator with high sensitivity for identifying the hyperacute ischemic stroke.

Orbital Indeterminate Lesions in Adults: Combined Magnetic Resonance Morphometry and Histogram Analysis of Apparent Diffusion Coefficient Maps for Predicting Malignancy.

RATIONALE AND OBJECTIVES The aim of this study was to evaluate the added value of histogram analysis of apparent diffusion coefficient (ADC) maps in differentiating indeterminate orbital malignant tumors from benign tumors, compared to using magnetic resonance (MR) morphological features alone. MATERIALS AND METHODS We retrospectively evaluated 54 patients with orbital tumors from March 2013 to February 2015. All the patients were assessed by both routine MR and diffusion-weighted imaging, and divided into benign group and malignant group. Routine MR imaging features and histogram parameters derived from ADC maps, including mean ADC (ADCmean), median ADC (ADCmedian), standard deviation, skewness, kurtosis, and 10th and 90th percentiles of ADC (ADC10 and ADC90), were compared between two groups. Univariate and multivariate logistic regression analyses were used to identify the most valuable variables in predicting malignancy. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of significant variables. RESULTS Multivariate logistic regression analysis indicated that two or more quadrants involved, iso-intense on T2-weighted imaging (T2WI), and ADC10 were significant predictors for orbital malignancy. By using model 2 (iso-intense on T2WI + two or more quadrants involved + ADC10 < 0.990) as the criterion, higher AUC and specificity could be achieved than by using model 1 (iso-intense on T2WI + two or more quadrants involved) alone, (model 2 vs model 1; area under curve (AUC), 0.827 vs 0.793; sensitivity, 65.4% vs 69.2%; specificity, 100% vs 89.3%). CONCLUSIONS Iso-intense on T2WI, two or more quadrants involved, and ADC10 are risk factors for orbital malignancy. Histogram analysis of ADC map might provide added value in predicting orbital malignancy.

An endovascular canine stroke model: middle cerebral artery occlusion with autologous clots followed by ipsilateral internal carotid artery blockade

Stroke is one of the leading causes of death worldwide and the main reason for long-term disability. An appropriate animal model of stroke is urgently required for understanding the exact pathophysiological mechanism of stroke and testing any new therapeutic regimen. Our work aimed to establish a canine stroke model occluding the middle cerebral artery (MCA) and blocking the ipsilateral internal carotid artery (ICA), and to assess the infarct lesions by magnetic resonance imaging. The stroke model was generated by injecting two autologous clots into each MCA, followed by 2-h ipsilateral ICA blockade (ilICAB) using a catheter in 15 healthy adult beagles. Outcome measurements included 24-h and 7-day postocclusion T2-weighted imaging (T2WI)-based infarct volume calculation. In addition, pial collateral score, canine neurobehavioral score and histopathologic results were documented. Out of 15 dogs, 12 with successful MCA occlusion (MCAO) and ilICAB survived 7 days without complications or casualties and MCA were reperfused at 7 days after occlusion. High signal intensity in the basal ganglia and cerebral cortex on T2WI was initially observed in each dog at 6 h after the procedure. The mean percentage hemispherical infarct volume corrected for edema in all dogs on T2WI at 24 h after occlusion was 12.99±1.57%, and the degree of variability was 12.08%. The infarct volumes at 24 h after occlusion correlated with pial collateral scores and canine neurobehavioral scores well. This canine stroke model with combined MCAO and ilICAB reported here were proven to be highly feasible and reproducible.

Follow-up of 58 traumatic carotid-cavernous fistulas after endovascular detachable-balloon embolization at a single center.

Background and Purpose This study evaluated the clinical value of detachable-balloon embolization for traumatic carotid-cavernous fistula (TCCF), focusing on the frequency, risk factors, and retreatment of recurrence. Methods Fifty-eight patients with TCCF underwent transarterial detachable-balloon embolization between October 2004 and March 2011. The clinical follow-up was performed every 3 months until up to 3 years postprocedure. Each patient was placed in either the recurrence group or the nonrecurrence group according to whether a recurrence developed after the first procedure. The relevant factors including gender, fistula location, interval between trauma and the interventional procedure, blood flow in the carotid-cavernous fistula, number of balloons, and whether the internal carotid artery (ICA) was sacrificed were evaluated. Results All 58 TCCFs were successfully treated with transarterial balloon embolization, including 7 patients with ICA sacrifice. Recurrent fistulas occurred in seven patients during the follow-up period. Univariate analysis indicated that the interval between trauma and the interventional procedure (p=0.006) might be the main factor related to the recurrence of TCCF. The second treatments involved ICA sacrifice in two patients, fistula embolization with balloons in four patients, and placement of a covered stent in one patient. Conclusions Detachable balloons can still serve as the first-line treatment for TCCFs and recurrent TCCFs despite having a nonnegligible recurrence rate. Shortening the interval between trauma and the interventional procedure may reduce the risk of recurrence.

Simple quantitative measurement based on DWI to objectively judge DWI-FLAIR mismatch in a canine stroke model

PURPOSE Diffusion-weighted imaging (DWI) - fluid attenuated inversion recovery (FLAIR) mismatch was proven useful to time the onset of wake-up stroke; however, identifying the status of FLAIR imaging has been mostly subjective. We aimed to evaluate the value of relative DWI signal intensity (rDWI), and relative apparent diffusion coefficient (rADC) in identifying the FLAIR status in the acute period. METHODS Autologous clot was used to embolize left middle cerebral artery in 20 dogs. Magnetic resonance imaging was performed 3-6 hours and 24 hours after embolization. DWI-FLAIR mismatch was defined as hyperintense signal detected on DWI, but not on FLAIR. The mean values of rDWI or rADC of FLAIR- and FLAIR+ lesions were compared and the critical cutoff values of rDWI and rADC for identifying the FLAIR status were determined. RESULTS Stroke models were successfully established in all animals. DWI+ lesions were found in all 20 dogs from three hours, while FLAIR+ lesions were found in three, 11, 16, 19, and 20 dogs at five time points after embolization, respectively. The mean rDWI values were significantly different between FLAIR- and FLAIR+ lesions (P < 0.001), but rADC values were not (P = 0.73). Using rDWI=1.90 as the threshold value, excellent diagnostic efficacy was achieved (AUC, 0.88; sensitivity, 0.77; specificity, 0.88). However, rADC appeared not useful (AUC, 0.48; sensitivity, 0.52; specificity, 0.58) in identifying the FLAIR status. CONCLUSION In our embolic canine stroke model, rDWI was useful to identify FLAIR imaging status in the acute period, while rADC was not.

Effects of regions of interest methods on apparent coefficient measurement of the parotid gland in early Sjögren's syndrome at 3T MRI.

Background The apparent diffusion coefficient (ADC) has been used to assess parotid gland abnormalities in Sjögren’s syndrome (SS) patients; however, few data exist on the influence of region of interest (ROI) methods on ADC measurements. Purpose To assess the influence of ROI methods on ADC measurement, and their diagnostic ability in detecting parotid gland abnormalities in early SS patients. Material and Methods Thirteen early SS patients underwent parotid gland diffusion-weighted imaging scans at a 3.0 T MR unit. Two readers independently measured the parotid gland ADC value using three different ROIs (whole-gland [WG], single-slice [SS], and reader-based circular [RBC]). The ADC value based on three different ROIs (ADC-ROIWG, ADC-ROISS, ADC-ROIRBC) were compared between the SS group and a matched healthy control (HC) group (n = 19). Receiver operating characteristic (ROC) curves and intra-class correlation coefficients (ICC) were used to determine the diagnostic ability and reproducibility of the parameters. Results The ADC-ROIWG, ADC-ROISS, and ADC-ROIRBC in the SS group were all significantly higher than those in HC group (all P < 0.05). The ADC-ROIWG showed better diagnostic ability than did ADC-ROIRBC (P = 0.0200), while no significant difference was found between ADC-ROIWG and ADC-ROISS (P = 0.4636). The ROIWG method showed the best inter- and intra-reader agreement (ICC, 0.902 and 0.928, respectively), followed by ROISS and ROIRBC. Conclusion The ROI methods can influence the parotid gland ADC measurements and their diagnostic ability. Considering our results, we suggest using in clinical practice single-slice ROIs to measure the ADC of the parotid gland.