MDSC-derived S100A8/9 contributes to lupus pathogenesis by promoting TLR7-mediated activation of macrophages and dendritic cells.

Toll-like receptors (TLRs), especially TLR7, play an important role in systemic lupus erythematosus (SLE) pathogenesis. However, the regulatory mechanism underlying the abnormal activation of TLR pathways in patients with SLE has not been elucidated. Notably, accumulating evidence indicates that myeloid-derived suppressor cells (MDSCs) are important regulators of inflammation and autoimmune diseases. Compared with healthy control subjects, patients with SLE have a greater proportion of MDSCs among peripheral blood mononuclear cells (PBMCs); however, the effect of MDSCs on TLR7 pathway activation has not been determined. In the present study, lupus MDSCs significantly promoted TLR7 pathway activation in macrophages and dendritic cells (DCs), exacerbating the imiquimod-induced lupus model. RNA-sequencing analysis revealed significant overexpression of S100 calcium-binding protein A8 (S100A8) and S100A9 in MDSCs from diseased MRL/lpr mice. In vitro and in vivo studies demonstrated that S100A8/9 effectively promoted TLR7 pathway activation and that S100A8/9 deficiency reversed the promoting effect of MDSCs on TLR7 pathway activation in lupus. Mechanistically, MDSC-derived S100A8/9 upregulated interferon gamma (IFN-γ) secretion by macrophages and IFN-γ subsequently promoted TLR7 pathway activation in an autocrine manner. Taken together, these findings suggest that lupus MDSCs promote TLR7 pathway activation and lupus pathogenesis through the S100A8/9-IFN-γ axis. Our study identified an important target for SLE therapy.

ACK1 Contributes to the Pathogenesis of Inflammation and Autoimmunity by Promoting the Activation of TLR Signaling Pathways.

Toll-like receptors (TLRs) are the first line of defense in the immune system, whose activation plays a key role in the pathogenesis of inflammation and autoimmunity. TLRs can activate a variety of immune cells such as macrophages and dendritic cells, which produce proinflammatory cytokines, chemokines, and co-stimulatory molecules that lead to the development of inflammation and autoimmune diseases. As a nonreceptor tyrosine kinase, ACK1 is involved in multiple signaling pathways and physiological processes. However, the roles of ACK1 in the activation of TLR pathways and in the pathogenesis of inflammation and autoimmune diseases have not yet been reported. We found that the expression of ACK1 could be upregulated by TLR pathways in vivo and in vitro. Intriguingly, overexpression of ACK1 significantly promoted the activation of TLR4, TLR7, and TLR9 pathways, while knockdown of ACK1 or the use of the ACK1 inhibitor AIM-100 significantly inhibited the activation of TLR4, TLR7, and TLR9 pathways. In vivo studies showed that the inhibition of ACK1 activity by AIM-100 could significantly protect mice from the TLR4 agonist lipopolysaccharide (LPS)-mediated endotoxin shock and alleviate the condition of imiquimod-mediated lupus-prone mice and MRL/lpr mice. In summary, ACK1 participates in TLR-mediated inflammation and autoimmunity and has great potential in controlling inflammation and alleviating autoimmune diseases.

Arctigenin inhibits abnormal germinal center reactions and attenuates murine lupus by inhibiting IFN-I pathway.

Interferon-I (IFN-I) signaling pathway plays a vital role in the differentiation of germinal center B cells and the pathogenesis of systemic lupus erythematosus (SLE). Therefore, targeting the IFN-I signaling pathway could serve as an effective treatment strategy in SLE. Arctigenin is an active ingredient present in the seeds of Arctium lappa L. It has been reported to act as a negative regulator of inflammatory responses. However, the role of arctigenin remains unknown in the regulation process of the IFN-I-mediated differentiation of germinal center B cells and the pathogenesis of SLE. In the present study, we demonstrated that arctigenin alleviated the progression of spontaneous lupus in MRL/lpr mice and imiquimod-mediated lupus mice. Especially, arctigenin significantly reduced the proportions of germinal center B cells (7.1%, vs. 5.12%, p < 0.01), follicular helper T cells (11.49%, vs. 5.53%, p < 0.05), and plasma cells (2.44%, vs. 1.39%, p < 0.01) in the lupus-prone mice. In vitro studies have shown that arctigenin significantly inhibited the IFN-α-induced CD69 and interferon-stimulated gene (ISG) expressions along with the phosphorylation of JAK1 and STAT1 by nearly half in murine B cells via activating PP2A. Overall, these data highlighted the role of arctigenin in regulating the IFN-I-mediated differentiation of germinal center B cells and the pathogenesis of SLE. Thus, arctigenin may be used as a potentially effective therapeutic target for the treatment of SLE.

Pyruvate Kinase M2 Contributes to TLR-Mediated Inflammation and Autoimmunity by Promoting Pyk2 Activation.

Toll-like receptors (TLRs) play critical roles in regulating the abnormal activation of the immune cells resulting in the pathogenesis of inflammation and autoimmune diseases. Pyruvate kinase M2 (PKM2), which governs the last step of glycolysis, is involved in multiple cellular processes and pathological conditions. However, little is known about the involvement of PKM2 in regulating TLR-mediated inflammation and autoimmunity. Herein, we investigated the role of PKM2 in the activation of the TLR pathways and the pathogenesis of inflammation and autoimmune diseases. The activation of TLR4, TLR7 and TLR9 pathways was found to induce the up-regulation of PKM2 expression in macrophages, dendritic cells (DCs) and B cells. The over-expression of PKM2 promotes the activation of TLR4, TLR7 and TLR9 pathways while interference with the PKM2 expression or the addition of the PKM2 inhibitor (PKM-IN) markedly inhibited the activation of TLR4, TLR7 and TLR9 pathways. Mechanistically, PKM2 augmented the activation of TLR4, TLR7 and TLR9 pathways by promoting the activation of the proline-rich tyrosine kinase 2 (Pyk2). Intriguingly, the PKM2 inhibitor PKM2-IN significantly protected the mice from the endotoxic shock mediated by the TLR4-agonist LPS. Additionally, it alleviated the progression in the TLR7-agonist imiquimod-mediated lupus mice and spontaneous lupus MRL/lpr mice. Moreover, PKM2 expression was highly elevated in the monocytes, DCs and B cells from systemic lupus erythematous (SLE) patients compared with those from the healthy donors. Besides, the PKM2 expression level was positively correlated with the degree of activation of these immune cells. In summary, PKM2 contributed to TLR-mediated inflammation and autoimmunity and can be a valuable target to control inflammation and autoimmunity.

Are prominent medullary veins better than prominent cortical veins as predictors of early clinical outcome in patients with acute ischemic stroke?

PURPOSE: The prominent vessel sign (PVS) on susceptibility-weighted imaging (SWI) can be dichotomized into prominent cortical veins (PCV) and prominent medullary veins (PMV). This study was designed to compare the predictive value of PCV and PMV in the evaluation of the severity of acute ischemic stroke (AIS) in patients within the reperfusion window. METHODS: Forty-seven consecutive patients with AIS within the middle cerebral artery territory were recruited. Magnetic resonance imaging was performed within 8 hours of symptom onset and at 7 days after stroke onset. Infarct volume was measured, and the early clinical outcome at 7 days was assessed using the modified Rankin Scale. PVS was dichotomized into cases with both PCV and PMV and cases with only PCV according to location. RESULTS: Patients with both PCV and PMV (n=32) had higher admission National Institutes of Health Stroke Scale scores (p = 0.020), larger infarct volumes at baseline (p = 0.026) and 7 days (p = 0.007), and larger infarct growth at 7 days (p = 0.050) than those with PCV only. Multivariate regression analysis showed that both the time of onset at baseline (p = 0.013) and infarct growth at 7 days (p = 0.014) could independently predict poor early clinical outcome. CONCLUSION: PMV may predict poor early clinical outcome in AIS patients, and reperfusion therapy may, therefore, be required more urgently in patients with PMV.

Comparison of three FLAIR vascular hyperintensities methodologies in patients with acute ischemic stroke.

BACKGROUND: Multiple methods have been used to analyze fluid-attenuated inversion recovery (FLAIR) vascular hyperintensities (FVHs) which may represent collaterals in patients with acute ischemic stroke (AIS); however, there is no consensus between methods. PURPOSE: To compare three frequently used FVH methods for predicting early infarct volume and clinical outcome in patients with AIS. MATERIAL AND METHODS: Patients with AIS in middle cerebral artery territory were recruited. FVHs were evaluated using extensive FVHs, FVH-diffusion-weighted imaging (DWI) mismatch, and FVH-in/out-DWI. Infarct volume at baseline and day 7 were measured. Early neurological improvement (ENI) was assessed. Good outcomes were defined by modified Rankin Scale scores of 0-2 at 90 days. RESULTS: Fifty-one patients were included. ENI was 55.6% in patients with extensive FVHs and 23.3% in those without (P = 0.024). Patients with extensive FVHs had smaller infarct volume growth at seven days than those without (P = 0.041). ENI was 48.3% in patients with FVH-DWI mismatch and 15.8% in those without (P = 0.021). Patients with FVH-DWI mismatch had smaller infarct volumes at seven days than those without (P = 0.038). Patients with FVH-out-DWI had smaller baseline infarct volumes, smaller seven-day volumes, and smaller infarct growth than those with FVH-in-DWI (P<0.001, P<0.001, and P = 0.031, respectively). In multivariate logistic regression analysis, the infarct growth at seven days negatively independently predicted ENI (OR = 0.737, 95% CI 0.593-0.915, P = 0.006). However, none of the FVH classifications could predict a good 90-day outcome. CONCLUSION: Patients with extensive FVHs or FVH-DWI mismatch tend to have early favorable clinical outcome. FVH-out-DWI being associated with smaller infarct growth may also indicate early favorable clinical outcome.

Nanodiamond phantoms mimicking human liver: perspective to calibration of T1 relaxation time in magnetic resonance imaging.

Phantoms of biological tissues are materials that mimic the properties of real tissues. This study shows the development of phantoms with nanodiamond particles for calibration of T1 relaxation time in magnetic resonance imaging. Magnetic resonance imaging (MRI) is a commonly used and non-invasive method of detecting pathological changes inside the human body. Nevertheless, before a new MRI device is approved for use, it is necessary to calibrate it properly and to check its technical parameters. In this article, we present phantoms of tissue with diamond nanoparticles dedicated to magnetic resonance calibration. The method of producing phantoms has been described. As a result of our research, we obtained phantoms that were characterized by the relaxation time T1 the same as the relaxation time of the human tissue T1 = 810.5 ms. Furthermore, the use of diamond nanoparticles in phantoms allowed us to tune the T1 value of the phantoms which open the way to elaborated phantoms of other tissues in the future.

Characteristics of Wall Shear Stress and Pressure of Intracranial Atherosclerosis Analyzed by a Computational Fluid Dynamics Model: A Pilot Study.

Background: Although wall shear stress (WSS) and pressure play important roles in plaque vulnerability, characteristics of the two indices in intracranial atherosclerosis (ICAS) have not been fully investigated yet. This study aimed to elucidate this issue by means of establishing a non-invasive computational fluid dynamics method with time-of-flight magnetic resonance angiography (TOF-MRA) of the whole cerebral artery. Materials and Methods: Subjects with symptomatic ICAS in the middle cerebral artery domain were enrolled, excluding those with concomitant internal carotid artery stenosis. Based on patient-specific TOF-MRA images for three-dimensional (3D) meshes and arterial blood pressure with patient-specific carotid artery ultrasonography for inlet boundary conditions, patients' three-dimensional hemodynamics were modeled by a finite element method governed by Navier-Stokes equations. Results: Among the 55 atherosclerotic lesions analyzed by this TOF-MRA based computational fluid dynamics model, the maximum WSS (WSSmax) was most frequently detected at the apex points and the upper half of the upstream sections of the lesions, whereas the maximum pressure was most often located at the lower half of the upstream sections. As the percent stenosis increases, the relative value of WSSmax and pressure drop increased with significantly increasing steep beyond 50% stenosis. Moreover, WSSmax was found to linearly correlate with pressure drop in ICAS. Conclusions: This study on ICAS revealed certain trends of longitudinal distribution of WSS and pressure and the influences of percent stenosis on cerebral hemodynamics, as well as the correlations between WSS and pressure drop. It represents a step forward in applying computational flow simulation techniques in studying ICAS and stroke, in a patient-specific manner.

Combined diagnosis of breast cancer in the early stage by MRI and detection of gene expression.

Breast cancer is one of the most common cancer types in humans. Magnetic resonance imaging (MRI) is an efficient method for the detection of human breast cancer. However, the efficacy of MRI in detecting breast cancer in the early stage requires to be improved. The present study investigated the diagnostic efficacy of a combination of MRI and detection of gene expression in patients with breast cancer in the early stage. The gene expression levels of Ki-67, BCL11A, FOXC1, HOXD13, PCDHGB7 and her-2 were used as an auxiliary diagnostic index for patients with breast cancer in the early stage. Higher expression levels of TPA and C2erbB22 were observed in tumor tissue obtained from diagnostic biopsy and determined by immunohistochemistry, which indicated a higher risk of breast cancer in a total of 84 participants. Diagnostic data revealed that combination MRI and detection of gene expression had a significantly higher diagnostic rate (66/84) in diagnosing breast cancer in an early stage compared with either MRI (78/360) or detection of gene expression (72/84; P<0.01). It was indicated that the combination of MRI and detection of gene expression had a higher diagnostic rate (94.5%) than either MRI (81.4%) or detection of gene expression (75.5%). Histological analysis confirmed the diagnosis determined by MRI and detection of gene expression. These results suggest that the combination of MRI and detection of gene expression may be a potential diagnostic method for assessing patients with early-stage breast cancer.

Middle Cerebral Artery Atherosclerosis and Deep Subcortical Infarction: A 3T Magnetic Resonance Vessel Wall Imaging Study.

BACKGROUND: Deep subcortical infarction is a major subtype of stroke in middle cerebral artery (MCA) territory. This study aims to evaluate the relationship between characteristics of MCA plaque and features of deep subcortical infarction. METHODS: Patients with recent acute ischemic stroke and deep subcortical infarction were prospectively enrolled. Both multicontrast brain sequences and 3D high-resolution vessel wall imaging (VWI) sequences were scanned for all patients. MCA plaque characteristics, including plaque presence, location, maximum vessel wall thickness (Max WT), signal intensity and luminal stenosis, and deep subcortical infarction features, including lowest infarct layer index (LILI), area, volume, maximum area, and infarct quantity were evaluated. Infarct feature differences were compared between MCA plaque+ group and MCA plaque- group. The correlations between MCA plaque characteristics and deep subcortical infarction features were analyzed. RESULTS: Of all 50 patients included in this study, 30 (60%) had MCA plaques. All deep subcortical infarction was single lesion for patients without MCA plaque. The average number of deep subcortical infarction for patients with MCA plaque was 3.10 ± 4.44. The LILI (P = .036) and infarct quantity (P = .030) showed significant differences between 2 groups. Max WT (P = .025) and stenosis degree (P = .023) were negatively correlated with LILI. Intraplaque hemorrhage was positively correlated with maximum area (P = .029) and infarct volume (P = .030). CONCLUSIONS: MCA plaque characteristics were correlated with deep subcortical infarct features. Magnetic resonance VWI may provide more information for etiological evidence of deep subcortical infarction.

NPR-9 regulates the innate immune response in Caenorhabditis elegans by antagonizing the activity of AIB interneurons.

npr-9 encodes a homologue of the gastrin-releasing peptide receptor (GRPR) and is expressed in AIB interneurons. In this study, we investigated the role of NPR-9 in the neuronal control of innate immunity using the model system Caenorhabditis elegans. After exposure to Pseudomonas aeruginosa PA14, npr-9(tm1652) mutants showed resistance to infection, decreased PA14 colonization and increased expression of immunity-related genes. Nematodes overexpressing NPR-9 exhibited increased susceptibility to infection, increased PA14 colonization and reduced expression of immunity-related genes. In nematodes, ChR2-mediated AIB interneuron activation strengthened the innate immune response and decreased PA14 colonization. Overexpression of NPR-9 suppressed the innate immune response and increased PA14 colonization in nematodes with the activation of AIB interneurons mediated by ChR2 or by expressing pkc-1(gf) in AIB interneurons. We, therefore, hypothesize that NPR-9 regulates the innate immune response by antagonizing the activity of AIB interneurons. Furthermore, expression of GRPR, the human homologue of NPR-9, could largely mimic NPR-9 function by regulating innate immunity in nematodes. Our results provide insight into the pivotal role of interneurons in controlling innate immunity and the complex biological functions of GRPRs.

Subject-Specific Fully-Coupled and One-Way Fluid-Structure Interaction Models for Modeling of Carotid Atherosclerotic Plaques in Humans.

BACKGROUND: Hemodynamics play an important role in the development and progression of carotid atherosclerosis, and may be important in the assessment of plaque vulnerability. The aim of this study was to develop a system to assess the hemodynamics of carotid atherosclerotic plaques using subject-specific fluid-structure interaction (FSI) models based on magnetic resonance imaging (MRI). MATERIAL AND METHODS: Models of carotid bifurcations (n=86 with plaques from 52 patients, n=14 normal carotids from 12 participants) were obtained at the Department of Radiology, Beijing Tian Tan Hospital between 2010 and 2013. The maximum von Mises stress, minimum pressure, and flow velocity values were assessed at the most stenotic site in patients, or at the carotid bifurcations in healthy volunteers. Results of one-way FSI were compared with fully-coupled FSI for the plaques of 19 randomly selected models. RESULTS: The maximum von Mises stress and the minimum pressure and velocity were significantly increased in the stenosis group compared with controls based on one-way FSI (all P<0.05). The maximum von Mises stress and the minimum pressure were significantly higher and the velocity was significantly lower based on fully coupled FSI compared with on-way FSI (all P<0.05). Although there were differences in numerical values, both methods were equivalent. The maximum von Mises stress of vulnerable plaques was significantly higher than stable plaques (P<0.001). The maximum von Mises stress of the group with fibrous cap defect was significantly higher than the group without fibrous cap defect (P=0.001). CONCLUSIONS: The hemodynamics of atherosclerotic plaques can be assessed noninvasively using subject-specific models of FSI based on MRI.

Distribution and features of middle cerebral artery atherosclerotic plaques in symptomatic patients: a 3.0 T high-resolution MRI study.

OBJECTIVES: To investigate the distribution and features of middle cerebral artery (MCA) atherosclerotic plaques in patients with acute ischaemic strokes using high-resolution magnetic resonance (MR) imaging. METHODS: Forty-six plaques from 44 MCAs (18 right and 26 left) in patients with acute symptomatic ischaemic strokes were studied. High-resolution MR imaging including tb1 weighted imaging (T1WI), tb2 weighted imaging (T2WI), PD weighted imaging (PDWI) and three-dimensional magnetization-prepared rapid acquisition gradient-echo (MPRAGE) sequences were used to visualise the plaques. The locations of plaques were classified into ventral, distal, superior and inferior wall of the MCA on oblique sagittal images. The thickness, area and signal intensities of plaques were recorded. The stenosis degree of MCA was calculated. RESULTS: Among all 46 plaques, 26 plaques were located at the ventral wall (56.5%), 6 at the dorsal wall (13.0%), 9 at the superior wall (19.6%), and five at the inferior wall (10.9%). The average thickness and area of plaques were 1.37 ± 0.53 mm (range: 0.61-3.20 mm) and 3.80 ± 2.13 mm(2) (range: 1.01-12.2 mm(2)), respectively. No significant differences in plaque thickness (P = 0.464), plaque area (P = 0.107) or stenosis degree (P = 0.563) were noted between different locations. Most of the plaques (44/46) showed iso-intensity on tbl1WI. On tbl2WI and PDWI, 24 plaques showed iso-intensity, 12 plaques showed a slightly high signal intensity (SI), and eight plaques showed a slightly low SI. Intraplaque haemorrhage was found in two plaques, with high SI on tbl1WI and MP-RAGE and high or mixed SI on tbl2WI and PDWI. DISCUSSION: Middle cerebral artery plaques in patients with acute infarction have certain tendency to locate at ventral and superior walls. Distribution and features of plaques revealed some plaque formation characteristics and would help to understand underlying mechanisms of ischaemic events.

Hemodynamic parameters distribution of upstream, stenosis center, and downstream sides of plaques in carotid artery with different stenosis: a MRI and CFD study.

BACKGROUND: Histopathological studies have shown significant differences in plaque components and surface conditions between upstream and downstream of the stenosis. It can be deduced that the flow status near the plaques is different from the flow status at the upstream side, stenosis center, or downstream side of the plaque. PURPOSE: To study the hemodynamic parameter distribution in different locations near atherosclerotic plaques in the carotid arteries with different stenosis degrees. MATERIAL AND METHODS: Eleven patients were recruited in this study. CE-MRA was performed to obtain the carotid three-dimensional surface data and the stenosis degrees were calculated. The hemodynamic parameters including wall shear stress (WSS), pressure, and velocity near the plaques were obtained by computational fluid dynamic (CFD) method. Local hemodynamics parameters were analyzed and compared between different stenosis degree groups, and between upstream, stenosis center, and downstream sides of plaques. Relative ratio of velocity, WSS, and pressure values in different locations was calculated and compared. RESULTS: Fourteen carotid arteries (with 4 mild, 6 moderate, and 4 severe stenosis) were analyzed. Significant differences were found in Pressure max (P = 0.025), Pressure mean (P = 0.020), and Pressure min (P = 0.026) between three stenosis groups. It showed significant differences in Vmin (P < 0.001) and WSSmin (P < 0.001) between three different locations. It showed upstream to downstream ratio of WSSmax (P = 0.034) and WSSmean value (P = 0.042) was significantly different between mild and moderate/severe groups. Significant differences were found in upstream to stenosis center ratio of Pressure max value (P = 0.018), Pressure mean value (P = 0.029), and Pressure min value (P = 0.026), as well as in stenosis center to downstream ratio of Pressure min value (P = 0.042). CONCLUSION: Velocity, WSS, pressure, and relative ratio of these parameters have certain trends in distribution around the plaques in the carotid arteries.

Association of plaque compositions and stenosis patterns in carotid bifurcation using MR imaging.

OBJECTIVES: To investigate the relationship between plaque compositions and stenosis patterns in patients with atherosclerotic plaques at the carotid bifurcation using magnetic resonance (MR) imaging. METHODS: One hundred and four carotid arteries with stenosis over 50% from 75 symptomatic stroke patients (64 male and 11 female; mean age 58·2±13·3 years) were studied. Plaque compositions were analyzed by high-resolution MR imaging using a 3·0T MR with a surface coil. Stenosis patterns were classified into three types according to contrast-enhanced MR angiography images. Correlations of different components of plaques and stenosis patterns were analyzed. RESULTS: One hundred and four carotid arteries were analyzed. Three stenosis patterns were identified. The prevalences of the three patterns are as follows: type I (total occlusion) at 27·9% (29/104), type II (local plaque with normal distant flow) at 56·7% (59/104), and type III (local plaque with impaired distant flow) at 15·4% (16/104). The contingency coefficients between stenosis pattern and stability, intraplaque hemorrhage (IPH), lipid necrotic core (LNC), and ulcer were 0·383 (P = 0·000), 0·290 (P = 0·008), 0·439 (P = 0·000), and 0·388 (P = 0·000), respectively. Multinomial analysis showed that compared with type III vessels, type I vessels were more likely to contain IPH (P = 0·019) and less likely to contain large LNC (P = 0·001); type II vessels had a greater possibility for containing IPH than type III vessels (P = 0·009); LNC was more likely to be found in type II than in type I vessels (P = 0·000). No significant difference was found in ulceration prevalence between type II and type III vessels (P = 0·058). CONCLUSIONS: The current study demonstrated positive associations between stenosis patterns and plaque compositions.

Association between cerebral microbleeds and the first onset of intracerebral hemorrhage - a 3.0 T MR study.

BACKGROUND: Cerebral microbleeds (CMBs) detected by gradient-echo MRI have been proven to be a potential risk factor for further bleeding, while the association between CMBs and the first onset of intracerebral hemorrhage has not been well investigated. PURPOSE: To analyze the association between CMBs and the first onset of primary intracerebral hemorrhage (pICH). MATERIAL AND METHODS: Two hundred and two consecutive inpatients with ICH and 234 consecutive outpatients without ICH as control group were enrolled in this study. MR imaging including T2*-GRE, T(1)W, T(2)W and fluid attenuated inversion recovery (FLAIR) sequences were performed to detect CMBs and other abnormalities. Prevalence, distribution, and grades of CMBs, as well as the location and size of the intracerebral hematoma were analyzed, respectively. Comparison was made between pICH and control group. Logistic analysis was performed to evaluate the association between CMBs and ICH. The correlation between hematoma size and CMBs grade/numbers was analyzed. RESULTS: CMBs were detected in 140 patients in pICH (69.3%) group and 62 patients in control group (26.5%). The incidence of CMBs in pICH group was significantly higher than that in control group (P < 0.0001). As the logistic regression analysis results, CMBs was the risk factor associated with ICH, with modulation OR value of 8.363 (95% CI 5.210-13.421). The volume of ICH with CMBs was 12.57 ± 17.23 mL, and the volume of ICH without CMBs was 17.77 ± 26.97 mL. Negative correlation was demonstrated between CMBs number and ICH volume (r(s) = -0.1769, P = 0.0118), as well as between CMBs grade and hematoma volume (r(s) = -0.1185, P = 0.1557). CONCLUSION: CMBs may be an independent risk factor for the first onset of intracerebral hemorrhage.

Distribution of wall shear stress in carotid plaques using magnetic resonance imaging and computational fluid dynamics analysis: a preliminary study.

BACKGROUND: Wall shear stress is an important factor in the destabilization of atherosclerotic plaques. The purpose of this study was to assess the distribution of wall shear stress in advanced carotid plaques using high resolution magnetic resonance imaging and computational fluid dynamics. METHODS: Eight diseased internal carotid arteries in seven patients were evaluated. High resolution magnetic resonance imaging was used to visualize the plaque structures, and the mechanic stress in the plaque was obtained by combining vascular imaging post-processing with computational fluid dynamics. RESULTS: Wall shear stresses in the plaques in all cases were higher than those in control group. Maximal shear stresses in the plaques were observed at the top of plaque hills, as well as the shoulders of the plaques. Among them, the maximal shear stress in the ruptured plaque was observed in the rupture location in three cases and at the shoulder of fibrous cap in two cases. The maximal shear stress was also seen at the region of calcification, in thrombus region and in the thickest region of plaque in the other three cases, respectively. CONCLUSION: Determination of maximal shear stress at the plaque may be useful for predicting the rupture location of the plaque and may play an important role in assessing plaque vulnerability.

Effect of baseline magnetic resonance imaging (MRI) apparent diffusion coefficient lesion volume on functional outcome in ischemic stroke.

OBJECTIVE: We explored the relationship between predicted infarct core, predicted ischemic penumbras and predicted final infarct volumes obtained though apparent diffusion coefficient (ADC)-based method, as well as other clinical variables, and functional outcome. METHODS: Patients with acute cerebral ischemic stroke were retrospectively recruited. The National Institutes of Health Stroke Scale score was evaluated at baseline and the modified Rankin Scale (mRS) at day 90. Favorable outcome was defined as an mRS score of 0 to 2, and unfavorable outcome as 3 to 6. Multimodal stroke magnetic resonance imaging was carried out at presentation. The volumes of diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) were measured using the regions of interest (ROI) method. The volumes of predicted infarct core, predicted ischemic penumbra and predicted final infarct were obtained by an automated image analysis system based on baseline ADC maps. The association between baseline magnetic resonance imaging volumes, baseline clinical variables, and functional outcome was statistically analyzed. RESULTS: The study included 30 males and 20 females (mean±SD age, 56±10 years). Baseline DWI, PWI and PWI-DWI mismatch volumes were not correlated with day-90 mRS (P>0.05). Predicted infarct core, predicted ischemic penumbra and predicted final infarct through ADC-based method were all correlated with day-90 mRS (P<0.05). A better outcome was associated with a smaller predicted volume. Low baseline National Institutes of Health Stroke Scale and recanalization also demonstrated a trend toward a favorable outcome. Receiver operating characteristic analysis showed that the area under the curve of predicted final infarct volume and recanalization were higher with statistical significance (P<0.001). DISCUSSION: Predicted volumes obtained from ADC-based methods, especially predicted final infarct volume, as well as baseline National Institutes of Health Stroke Scale and recanalization may have effect on functional outcome in acute ischemic stroke.

Prediction of infarct core and salvageable ischemic tissue volumes by analyzing apparent diffusion coefficient without intravenous contrast material.

RATIONALE AND OBJECTIVES: To investigate whether baseline apparent diffusion coefficient (ADC) maps can be employed to predict both infarct core and salvageable ischemic tissue volumes in acute ischemic stroke. MATERIALS AND METHODS: An automated image analysis system based on baseline ADC maps was tested against 30 patients with acute ischemic stroke of anterior circulation to predict both infarct core and salvageable ischemic tissue volumes. The predicted infarct core and predicted salvageable ischemic tissue were quantitatively and qualitatively compared with follow-up imaging data in recanalization and no recanalization groups, respectively. Direct comparisons with perfusion- and diffusion- weighted magnetic resonance imaging measures were also made. Wilcoxon signed-rank test, Spearman rank correlation, and Bland-Altman plots were performed. RESULTS: In the recanalization group, the predicted infarct core volume was significantly correlated with the final infarct volume (r = 0. 868, P < .001). In the no recanalization group, the predicted final infarct volume (sum of the predicted infarct core and salvageable ischemic tissue volumes), as well as the predicted salvageable ischemic tissue volume, was also significantly correlated with the true final infarct volume (r = 0.955, P < .001) and infarct growth (r = 0.918, P < .001), respectively. The volumes of perfusion-diffusion mismatch were significantly larger than those of infarct growth and predicted salvageable ischemic tissue. Good agreement between predicted and true final infarct lesions was visualized by Bland-Altman plots in two groups. Direct visual comparative analysis revealed good qualitative agreement between the true final infarct and predicted lesions in 21 patients. CONCLUSION: The proposed ADC based approach may be a feasible and practical tool to predict the volumes of infarct core and salvageable ischemic tissue without intravenous contrast media-enhanced perfusion-weighted imaging at baseline.