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This study aimed to investigate the enhancement characteristics of vessel wall in patients with moyamoya disease (MMD) using 3D high-resolution magnetic resonance (MR) imaging and their relationship with initial and recurrent intracranial hemorrhage. Consecutive patients with MMD were retrospectively analyzed and classified as intracranial hemorrhagic and non-hemorrhagic groups according to the CT or MR images. The clinical features and vessel wall characteristics were compared between the two groups. Logistic regression was performed to relate the vessel wall characteristics to the initial hemorrhage in MMD patients. Patients in hemorrhagic group were followed up after surgery to evaluate the relationship between vessel wall characteristics and recurrent hemorrhage. A total of 507 MMD patients including 79 hemorrhagic and 428 non-hemorrhagic MMD patients were recruited in the study. We found that hemorrhagic group had more patients with vessel wall enhancements (40.5% vs. 25.7%, p = 0.009) and more eccentric enhanced lesions (17.7% vs. 6.5%, p = 0.001) compared to those in non-hemorrhage group and vessel wall enhancements were independently associated with ipsilateral initial hemorrhage after adjusted for clinical factors (OR = 1.99, CI 1.20–3.28, p = 0.007). Furthermore, three recurrent intracranial hemorrhagic episodes in the present study were all observed in MMD patients with vessel wall enhancement during the long-term follow-up after surgery. Wall enhancement of intracranial vessels was significantly associated with intracranial hemorrhage in MMD patients. Our findings suggest that vessel wall enhancement may serve as a marker of intracranial hemorrhage.

BACKGROUND Carotid vulnerable plaque is a major cause of stroke and differs between men and women. Few studies have investigated the differences in carotid plaque features between sexes in a Chinese population. PURPOSE To compare carotid atherosclerotic plaque features between men and women in a Chinese population using magnetic resonance imaging. STUDY TYPE Cross-sectional. SUBJECTS A total of 567 patients (mean age: 61.5 ± 10.1 years; 404 men) who had recent stroke or transient ischemia attack and atherosclerotic plaque in at least one carotid artery. FIELD STRENGTH A 3.0 T. SEQUENCE T1- and T2-weighted turbo spin echo, three-dimensional time-of-flight (TOF) fast field echo and magnetization-prepared rapid acquisition gradient echo sequences. ASSESSMENT Plaque characteristics including lumen area (LA), wall area (WA), total vessel area (TVA), mean wall thickness (MWT), and mean normalized wall index (NWI); presence of calcification, lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), and fibrous cap rupture (FCR); and percent composition area (%area) were evaluated and compared between men and women. STATISTICAL TESTS Independent-sample t test, Mann-Whitney U test, chi-square test, and multiple linear and logistic regressions. RESULTS In symptomatic arteries, men had significantly greater LA (46.2 ± 15.6 mm2 vs. 40.7 ± 12.9 mm2 , P

Purpose:This study aimed to compare the characteristics of carotid plaques between patients with transient ischemic attack (TIA) and ischemic stroke using magnetic resonance (MR) imaging.Methods：Symptomatic patients with carotid atherosclerotic plaque who had a recent ischemic stroke or TIA were recruited and underwent carotid MR imaging. The characteristics of plaque morphology and compositions including intraplaque hemorrhage (IPH), lipid-rich necrotic-core (LRNC) and calcification were compared between TIA and stroke patients. Logistic regression was performed to relate the plaque characteristics to the types of ischemic events.Results:A total of 270 patients with TIA or ischemic stroke were recruited. Stroke patients had significantly higher prevalence of diabetes (42.2% vs. 28.2%, p=0.021), greater mean wall area (35.1 ± 10.1 mm2 vs. 32.0 ± 7.7mm2, p = 0.004), mean wall thickness (1.3 ± 0.2 mm vs. 1.2 ± 0.2 mm, p=0.001), maximum normalized wall index (NWI)(63.9% ± 6.0% vs. 62.2% ± 5.9%, p=0.023)and %volume of LRNC(9.7%± 8.2% vs. 7.4% ±7.9%, p=0.025)in carotid arteries compared to those with TIA. After adjusted for clinical factors, above characteristics of carotid arteries were significantly associated with the type of ischemic events. After further adjusting for maximum NWI, the association of %volume of LRNC and stroke subtype remained statistically significant (OR, 1.41; CI, 1.01-1.96; p=0.041).Conclusions:Ischemic stroke patients had larger plaque burden and greater proportion of LRNC in symptomatic carotid plaques compared to patients with TIA. This study suggests that ischemic stroke patients had more vulnerable plaques compared to those with TIA.

Atherosclerosis in stroke-related vascular beds is the major cause of stroke. Studies demonstrated that multivascular atherosclerosis is prevalent in stroke patients and those with multivascular plaques had higher risk of recurrent stroke.This study investigated the relationship between homocysteine and multivascular atherosclerosis in stroke-related vascular beds using magnetic resonance imaging.Patients with recent ischemic cerebrovascular symptoms were enrolled and underwent three-dimensional magnetic resonance vessel wall imaging for intracranial arteries, extracranial carotid arteries and aortic arch. Traditional risk factors and homocysteine were measured. Presence of multivascular plaques defined as plaques in at least two stroke-related vascular beds on magnetic resonance imaging was determined. The relationship between homocysteine and characteristics of multivascular plaques was determined.Of 49 enrolled patients (mean age: 56.3 ± 13.8 years; 35 males), 23 had multivascular plaques. Homocysteine (odds ratio, 1.17; 95% confidence interval, 1.02-1.34; p = 0.022) and age (odds ratio, 1.71; 95% confidence interval, 1.22-2.41; p = 0.002) were significantly associated with presence of multivascular plaques. The adjusted associations remained significant (both p 0.05). In discriminating presence of multivascular plaques, the area-under-the-curve of age, homocysteine and combination of them was 0.79, 0.70 and 0.87 respectively.Homocysteine is independently associated with stroke-related multivascular plaques and combination of age and homocysteine has stronger predictive value.

This study aimed to investigate the segment-specific progression of atherosclerotic carotid plaques using serial multi-contrast magnetic resonance (MR) imaging. Symptomatic patients with carotid 30–70% stenosis were recruited and underwent carotid MR vessel wall imaging at baseline and follow-up time point (≥ 6 months after baseline). The location of plaques was determined according to the maximum wall thickness located above or below carotid bifurcation. The baseline and changing characteristics of carotid plaques were compared between plaques above and below carotid bifurcation, and the risk factors for segment-specific plaque progression were analyzed with logistic regression. Ninety-six carotid plaques from 73 patients (mean age 66.5 ± 11.4 years old) were eligible for statistical analysis. Compared with plaques located below carotid bifurcation, those above bifurcation had significantly greater stenosis at baseline (57.2 ± 13.0% vs. 50.4 ± 13.5%, p = 0.016, adjusted p = 0.005) and greater progression rate of carotid wall volume (35.2 ± 68.8 mm3/year vs. 4.2 ± 65.0 mm3/year, p = 0.026, adjusted p = 0.005) before and after adjusting for all clinical risk factors and baseline stenosis and wall volume of carotid arteries. Logistic regression showed that the related risk factors were age, hypertension, and smoke for the progression of plaques located above the bifurcation and age for plaques below the bifurcation, respectively. Plaques located above the bifurcation of carotid arteries had greater annual progression and correlated with more cardiovascular risk factors compared with those located below the bifurcation.

To explore the value of various diffusion parameters obtained from monoexponential, biexponential, and stretched exponential in assessing liver fibrosis in chronic hepatitis B (CHB). DWI and intravoxel incoherent motion (IVIM) MRI were performed prospectively on liver for 146 patients with CHB and 21 healthy volunteers. ADC values were obtained from monoexponential model imaging. Diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) obtained by biexponential model imaging, and stretched exponential model to obtain diffusion distribution coefficient (DDC) and diffusion heterogeneity index (α). Blood draw were performed on patients to obtain AST, ALT, and PLT, and then APRI and FIB-4 index were determined based on the serological diagnostic models. The fibrosis stage was staged (S0–S4) according to the pathology of liver puncture. Independent sample t test was used to compare the parameter values between liver fibrosis group and control group. One-way ANOVA was used to compare the parameters of different liver fibrosis grades. Bonferroni test was used for correcting multiple comparisons. Spearman correlation was used to analyze the correlation between each parameter and liver fibrosis grades. ROC was used to predict the diagnostic power of each parameter for liver fibrosis stages ≥ S2 and ≥ S3. ADC, D, D*, f, and DDC values were significantly different between normal control group and hepatic fibrosis group (P

Background and aims Dynamic contrast-enhanced MR imaging (DCE-MRI) provides a noninvasive approach to the functional status of carotid adventitial vasa vasorum . Contrast extravasation rate, or K trans , derived from kinetic modeling of adventitial enhancement, has been correlated with plaque neovascularization and inflammation. This study sought to clarify the clinical implications of K trans by evaluating its relationship with documented cardiovascular events (CVE). Methods Seventy patients with carotid plaque at clinical ultrasound examination were recruited and imaged with a previously-described bright-blood DCE-MRI protocol (spatial resolution: 0.55 × 0.58 mm 2 ; time resolution: 18 s). Patients were classified by the presence of documented coronary and/or cerebrovascular events. Adventitial K trans was estimated via kinetic modeling of outer wall enhancement as captured by DCE-MRI. Results After excluding six patients with insufficient image quality, 64 patients (66 ± 12 years, 51 male) had DCE-MRI measurements. Patients with documented CVE showed significantly higher adventitial K trans than those without (0.056 ± 0.024 versus 0.034 ± 0.008 min −1 , p p > 0.05): 0.054 ± 0.027 min −1 in patients with coronary events alone, 0.056 ± 0.018 min −1 in patients with cerebrovascular events alone, and 0.069 ± 0.022 min −1 in patients with both. Carotid adventitial K trans was negatively correlated with time since clinical event (Spearman's rho = −0.40, p = 0.003). Conclusions Patients with documented CVE demonstrated increased rate of contrast extravasation from carotid adventitial vasa vasorum on DCE-MRI irrespective of the territory of events. Systemic factors implicated in the pathophysiology of acute atherothrombotic events may influence the functional status of adventitial vasa vasorum .

Radiation‐induced lung injury (RILI) is one of the most common and fatal complications of thoracic radiotherapy. It is characterized with two main features including early radiation pneumonitis and fibrosis in later phase. This study was to investigate the potential radioprotective effects of polydatin (PD), which was shown to exert anti‐inflammation and anti‐oxidative capacities in other diseases. In this study, we demonstrated that PD‐mitigated acute inflammation and late fibrosis caused by irradiation. PD treatment inhibited TGF‐β1‐Smad3 signalling pathway and epithelial–mesenchymal transition. Moreover, radiation‐induced imbalance of Th1/Th2 was also alleviated by PD treatment. Besides its free radical scavenging capacity, PD induced a huge increase of Sirt3 in culture cells and lung tissues. The level of Nrf2 and PGC1α in lung tissues was also elevated. In conclusion, our data showed that PD attenuated radiation‐induced lung injury through inhibiting epithelial–mesenchymal transition and increased the expression of Sirt3, suggesting PD as a novel potential radioprotector for RILI.

The above article was published online with incorrect presentation of author name. Mingming is the given name and Lu is the family name. The presentation of the author name has been corrected above.

Background Statin therapy can improve plaque stability. However, the time course of effects of statin on adventitial angiogenesis and plaque neovascularization has not been studied. Objective The objective of the study was to investigate whether statin therapy reduces plaque neovascularization, associated with adventitial angiogenesis, over 24 months as assessed by using carotid dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Methods Forty-three lipid treatment–naive subjects with asymptomatic carotid atherosclerosis received rosuvastatin (5–20 mg/d) to lower low-density lipoprotein cholesterol to Results Adventitia Vp and adventitia Ktrans were significantly correlated with plaque Vp and plaque Ktrans at baseline. Rosuvastatin significantly reduced both adventitial and plaque Vp significantly at 3 months from 0.121 ± 0.064 to 0.085 ± 0.049 (P = .008) and from 0.096 ± 0.052 to 0.067 ± 0.043 (P = .013). Adventitial and plaque Vp continued to decrease by 43% and 34% at 12 months and by 49% and 45% at 24 months. However, the continued reductions from 3 to 12 months and from 12 to 24 months were not statistically significant. Adventitial and plaque Ktrans showed similar trends, but nonstatistically significant decreases during the 24 months of treatment. Conclusions Rosuvastatin therapy rapidly and significantly decreased adventitial and plaque neovascularization at 3 months followed by continued, but nonstatistically significant, decreases at 12 and 24 months.

This study aimed to investigate the association between age and progression of carotid atherosclerotic plaques using serial high resolution magnetic resonance imaging (MRI). Symptomatic patients who had carotid atherosclerosis with 30–70% stenosis were enrolled in this study. Carotid MRI was performed at baseline and follow-up time point (≥ 6 months after baseline), respectively. The characteristics of carotid plaque progression among different age groups (> 75 years old, 60–75 years old and 75 years old: 91.3%, 60–75 years old: 65.7% and 75 years old: 39.0 (4.3–104.6) mm3, 60–75 years old: 28.7 (− 28.0 to 73.7) mm3 and 75 years old: 6.1 (− 3.5 to 17.2) mm2, 60–75 years old: 2.4 (− 4.7 to 15.1) mm2 and

Background Different sensitivity of advanced cervical cancer to irradiation can decrease effectiveness of radiotherapy in some cases. We attempted to identify the differentially expressed genes in residual cervical cancer after radiotherapy that might be associated with poor prognosis and radioresistance. Material/Methods Differential genes expression was identified by an oligonucleotide microarray in cervical cancer tissues before radiation and after a 50-Gy dose of radiation. The microarray results were validated by quantitative real-time PCR. CXCL12 was validated by immunohistochemistry in paraffin-embedded cervical cancer tissues before radiotherapy. The relationship between the differentiated gene and prognosis was validated by survival analysis. Results Hierarchic cluster analysis identified 238 differentiated genes that exhibited ≥3.0-fold change and p

Background and Purpose— This study aimed to investigate the association between carotid plaque progression and subsequent recurrent events using magnetic resonance imaging. Methods— Sixty-three symptomatic patients with ipsilateral carotid atherosclerotic stenosis (30%–69% stenosis) determined by ultrasound underwent first and second carotid artery magnetic resonance imaging for carotid artery at baseline and ≥6 months after the first scan, respectively. All the patients had clinical follow-up after the second magnetic resonance scan for ≤5 years until the onset of recurrent transient ischemic attack or stroke. Presence/absence of carotid plaque compositional features, particularly intraplaque hemorrhage and fibrous cap rupture was identified. The annual progression of carotid wall volume between 2 magnetic resonance scans was measured. Univariate and multivariate Cox regression was used to calculate the hazard ratio and corresponding 95% confidence interval of carotid plaque features in discriminating recurrent events. Receiver-operating-characteristic-curve analysis was conducted to determine the area-under-the-curve of carotid plaque features in predicting recurrent events. Results— Sixty-three patients (mean age: 66.5±10.0 years old; 54 males) were eligible for final statistics analysis. During a mean follow-up duration of 55.1±13.6 months, 14.3% of patients (n=9) experienced ipsilateral recurrent transient ischemic attack/stroke. The annual progression of carotid wall volume was significantly associated with recurrent events before (hazard ratio, 1.14 per 10 mm 3 ; 95% confidence interval, 1.02–1.27; P =0.019) and after (hazard ratio, 1.19 per 10 mm3; 95% confidence interval, 1.03–1.37; P =0.022) adjusted for confounding factors. In discriminating the recurrence of transient ischemia attack/stroke, receiver–operator curve analysis indicated that combined with annual progression of wall volume, there was a significant incremental improvement in the area-under-the-curve of intraplaque hemorrhage (area-under-the-curve: 0.69–0.81) and fibrous cap rupture (area-under-the-curve: 0.73–0.84). Conclusions— The annual progression of carotid wall volume is independently associated with recurrent ischemic cerebrovascular events, and this measurement has added value for intraplaque hemorrhage and fibrous cap rupture in predicting future events.

Polymorphisms in X-ray cross-complementing group 3 (XRCC3) are proposed to be associated with cancer susceptibility, but previous studies on the associations between XRCC3 polymorphisms and thyroid cancer are controversial. We performed a systemic review and meta-analysis to investigate the associations of XRCC3 polymorphisms with thyroid cancer risk. We used odds ratio (OR) with 95 % confidence interval (95%CI) to assess the associations. For XRCC3 C241T polymorphism, meta-analysis of total eligible studies showed that there was no association between XRCC3 C241T polymorphism and thyroid cancer risk, but subgroup analysis in Caucasians showed that there was a significant association between XRCC3 C241T polymorphism and thyroid cancer risk (T versus C: OR = 1.30, 95%CI 1.05–1.62, P = 0.01; TT versus CC: OR = 1.74, 95%CI 1.13–2.70, P = 0.01; TT versus CC/CT: OR = 1.74, 95%CI 1.16–2.60, P = 0.007). For XRCC3 A17893G polymorphism, meta-analysis of total eligible studies showed that there was an obvious association between XRCC3 A17893G polymorphism and thyroid cancer risk (GG versus AA/AG: OR = 0.57, 95%CI 0.35–0.93, P = 0.02), but subgroup analysis by ethnicity only identify the significant association in Asians. In summary, the meta-analysis suggests that there are significant associations of XRCC3 polymorphisms with thyroid cancer risk. Besides, more studies with large sample sizes are needed to further assess the associations above.

Radiation therapy produced unwanted side effect on normal tissues, such as radiodermatitis. Hydrogen was previously shown capable of radiation protective in both animals and cell cultures. The effect of hydrogen was now to be investigated on radiation-induced cutaneous.Development of dermatitis is a frequent side effect of radiotherapy of patients with head-and-neck cancer. Here we analyzed the radioprotective efficacy of hydrogen under conditions of local, single-dose or fractionated radiation treatment, and its possible molecular mechanisms.Rats received either single-dose or fractioned irradiation of the head-and-neck area with or without subcutaneous injection of hydrogen solution before irradiation. In vitro, the effect of hydrogen medium on radiation-induced cell viability, apoptosis, and biochemical assays was measured.Hydrogen significantly reduced the severity of dermatitis, accelerated tissue recovery, and reduced the extent of radiation-induced weight loss in rats after a single dose of 15 or 20 Gy but not 25 Gy of radiation. Hydrogen was also protective from cumulative doses of 30 Gy delivered in three fractions, respectively. Hydrogen also protect HaCaT cells from radiation-induced injury, it could significantly inhibit ionizing injury.These results suggest that hydrogen has a positive effect on acute radiodermatitis.

// Chaoxiong Zhang 1, 2, * , Ning Wu 3, * , Fu Gao 1, * , Jiaqi Han 1 , Yanyong Yang 1 , Chuanfeng Zhou 1 , Weimin Sun 4 , Linfeng Xian 1 , Ying Cheng 1 , Bailong Li 1 , Jianming Cai 1 , Cong Liu 1 1 Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, 200433, PR China 2 Institute of Military Medicine, Chengdu Military Region, Chengdu, 610021, China 3 Department of Respiratory Medicine, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China 4 Department of Immunology, Second Military Medical University, Shanghai, 200433, People’s Republic of China * These authors contributed equally to this work Correspondence to: Jianming Cai, email: caijianming882003@163.com Cong Liu, email: victorliu20102020@163.com Keywords: MTERFD1, cancers, prognosis, proliferation, survival Received: October 02, 2015 Accepted: June 16, 2016 Published: August 09, 2016 ABSTRACT MTERFD1, also named MTERF3 (mitochondrial transcription termination factor 3), regulates transcription of the mitochondrial genome. MTERFD1 is a mitochondrial protein that represses mammalian mitochondrial DNA initiation in vivo . In this study, we found that MTERFD1 gene amplification and high expression existed in many different types of cancer. Significantly, increased expression of MTERFD1 gene was correlated with lower overall survival rate in clinical. Overexpression of MTERFD1 gene promoted to tumor cell growth in vivo and in vitro and increased the percentage of cells in S phase. In conclusion, our data firstly indicated the MTERFD1 was an oncogene in many types of cancer.

// Hu Liu 1, * , Shichao Wang 2, * , Zhao Wu 2, * , Ziyun Huang 2 , Wei you Chen 2 , Yanyong Yang 1 , Jianguo Cui 1 , Cong Liu 1 , Hainan Zhao 1 , Jiaming Guo 1 , Pei Zhang 1 , Fu Gao 1 , Bailong Li 1 and Jianming Cai 1 1 Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China 2 Fifth Cadet Battalion of Naval Medicine Department, Second Military Medical University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Fu Gao, email: gaofusmmu@163.com Bailong Li, email: libailong2003@163.com Jianming Cai, email: cjm882003@163.com Keywords: acute radiation-induced liver injury, reactive oxygen species (ROS), ATP-sensitive potassium channel (KATP), membrane potential (MP), glibenclamide Received: August 05, 2016 Accepted: February 15, 2017 Published: March 23, 2017 ABSTRACT Background: Acute radiation-induced liver injury is a limitation for hepatoma radiotherapy. Come so far the clinical treatments are insufficient. The effective, specific, low toxicity and novel drugs are in powerful need. Glibenclamide is a common hypoglycemic. Some studies have revealed its relation with intracellular reactive oxygen species, the crucial mediator to radiation injury. This study is aimed to investigate if glibenclamide could act on the acute radiation-induced liver injury. Results: Glibenclamide mitigated acute radiation-induced liver injury of mice, indicating as regression of hepatocellular edema, reduction of hepatic sinusoid, decline in serum ALP level and reduction of hepatocellular apoptosis. Pretreatment of glibenclamide reduced the radiosensitivity of NCTC-1469 cells. In mechanism, glibenclamide elevated cells membrane potential to up-regulate intracellular reactive oxygen species. The increased reactive oxygen species subsequently activated Akt–NF-κB pathway to promote survival of irradiated cells. Methods: BALB/C male mice were intraperitoneal injected with glibenclamide 1 hour before hepatic irradiation. At designed time points the livers were taken to make histological study and bloods were collected to measure serum transaminase. With/without glibenclamide pretreatment the irradiated NCTC-1469 cells were tested apoptosis, viability and proliferation. By western blotting the involved molecules were detected. Conclusions: Glibenclamide, prevents acute radiation-induced liver injury of mice via up-regulating intracellular reactive oxygen species and subsequently activating Akt–NF-κB pathway.

In recent years, people have been extending the concepts developed in quantum information science to explore quantum dynamics in biological systems. The existence of quantum coherence in certain biological processes has been identified in a number of experiments. The role of quantum coherence and quantum entanglement has been carefully investigated, which suggests that quantum effect is important in these processes although in a more complicated way. In the mean time, these findings urge the development of new experiment methodology to reveal more biological scenarios in which quantum effect exists and plays a non-trivial role. In this article, we review the latest progress in the field of quantum biology and discuss the key challenges in further development of quantum biology.

Molecular hydrogen (H2) has been previously reported playing an important role in ameliorating damage caused by acute radiation. In this study, we investigated the effects ofH2on the alterations induced by low-dose long-term radiation (LDLTR). All the mice in hydrogen-treated or radiation-only groups received 0.1 Gy, 0.5 Gy, 1.0 Gy, and 2.0 Gy whole-body gamma radiation, respectively. After the last time of radiation exposure, all the mice were employed for the determination of the body mass (BM) observation, forced swim test (FST), the open field test (OFT), the chromosome aberration (CA), the peripheral blood cells parameters analysis, the sperm abnormality (SA), the lymphocyte transformation test (LTT), and the histopathological studies. And significant differences between the treatment group and the radiation-only groups were observed, showing thatH2could diminish the detriment induced by LDLTR and suggesting the protective efficacy ofH2in multiple systems in mice against LDLTR.

Studies have shown that atherosclerosis in coronary arteries is closely related to that in carotid arteries, but there are few investigations on the correlation between unstable plaques in these 2 vascular beds. The authors aim to investigate the correlation between coronary plaque phenotype and carotid plaque composition.Patients (n = 123) with suspected coronary artery disease underwent computed tomography angiography of coronary arteries. Magnetic resonance imaging of bilateral carotid arteries was performed within 2 weeks after computed tomography angiography. The plaque type in each coronary segment was analyzed. Coronary plaques were classified into 3 types: noncalcified, calcified and mixed. The total number of each plaque type was scored. Carotid plaque with calcification, lipid-rich necrotic core (LRNC) or intraplaque hemorrhage (IPH) in either carotid artery was defined as positive. Logistic regression analysis was used to determine the correlation between coronary plaque phenotype and carotid plaque composition. The area under the receiver-operating characteristic curve (AUC) was calculated.There was a significant correlation between the mixed coronary plaque score and carotid IPH (odds ratio = 1.50, P0.05). The scores for all 3 types of the coronary plaque were significantly correlated with carotid LRNC and calcification. The mixed coronary plaque score had the highest value in predicting carotid IPH (AUC = 0.74). The calcified coronary plaque score showed the highest value in predicting carotid LRNC (AUC = 0.75) and calcification (AUC = 0.75).There was significant correlation between coronary plaque phenotype and carotid plaque composition. A mixed coronary plaque may be suggestive of a high-risk carotid plaque.

Bone marrow is a major site of radiation injury. The extreme sensitivity of bone marrow cells to genotoxic stress largely determines the adverse side effects of radiation. CpG-oligodeoxynucleotide (ODN) is known to be radioprotective in extramedullary hemopoiesis, but its effect on bone marrow hemopoiesis remains unknown. In this study, we investigated whether CpG-ODN ameliorated hemopoiesis radiation injury when administered after total-body irradiation (TBI). Mice were treated with 50 μg of CpG-ODN via intraperitoneal injection (i.p) 30 min., 24 and 48 hr after TBI. Our results show that CpG-ODN was able to mediate the activation of nuclear factor κB (NF-κB) via degradation of inhibitor NF-κB (IκB-α), and some oxidative stress parameters (malondialdehyde, glutathione and superoxide dismutase) showed significant differences between the radiation control group and the radiation and administration of CpG-ODN group. White blood cell count, bone marrow cell count and bone marrow histological examination indicated that CpG-ODN minimized bone marrow damage induced by radiation. Exogenous colony-forming unit-spleen count indicated that CpG-ODN reduced primitive hemopoietic stem cell damage and reconstituted the hemopoietic system after TBI. The survival of mice was also enhanced after various levels of TBI. The calculated dose reduction factor was 1.2. Thus, we conclude that CpG-ODN may contribute to the amelioration of hemopoiesis radiation injury.

The purpose of this study was to evaluate the differences in carotid arterial morphology and plaque composition between patients with acute coronary syndrome (ACS) and patients with stable coronary artery disease (SCAD). Twenty-eight patients (12 ACS patients and 16 SCAD patients) underwent carotid high-resolution MRI examination using a 3.0-Tesla (3.0T) MRI scanner. The indicators of carotid arterial morphology included the maximum total vessel area (Max-TVA), mean TVA, minimum lumen area (Min-LA), mean LA, maximum wall area (Max-WA), mean WA, maximum wall thickness (Max-WT), mean WT, maximum normalized wall index (Max-NWI), mean NWI, and maximum stenosis (Max-stenosis). The indicators of plaque composition included the prevalence and mean area percentage (%) of lipid-rich necrotic core (LRNC), calcification (Ca), intraplaque hemorrhage (IPH), and fibrous cap rupture (FCR). None of the indicators of carotid arterial morphology had significant differences (all P > 0.05) between the ACS and SCAD patients. The prevalence and plaque composition area percentage of LRNC, Ca, and IPH did not exhibit significant differences between the two groups. However, carotid plaques in the ACS patients presented a higher prevalence of FCR than SCAD patients (P < 0.05). This study revealed a similar carotid arterial morphology between ACS and SCAD patients. However, FCR is more common in carotid plaques with ACS than in those with SCAD. Ruptured carotid plaques may be a forewarning factor for those patients who are at high risk of ACS.

To evaluate the differences of signal evolution of intraplaque hemorrhage (IPH) and associated stenosis between symptomatic and asymptomatic atherosclerotic carotid arteries. Thirty-three carotid arteries (15 symptomatic and 18 asymptomatic plaques) with recent carotid IPH underwent serial high-resolution MRI examinations on a 3.0-Tesla (3.0T) MRI scanner over a period of 18 months. MR sequences included three-dimensional time-of-flight (3D-TOF), quadruple-inversion-recovery T1-weighted imaging (QIR T1 WI), proton density-weighted imaging (PDWI), and T2-weighted imaging (T2WI). The contrast-to-noise ratios (CNRs) of subsequent IPH during the follow-up period between symptomatic and asymptomatic carotid IPH showed a significant difference on 3D-TOF (P = 0.029), T1 WI (P = 0.005), and PDWI (P = 0.028), except for that on T2WI (P = 0.362). Compared with no significant signal intensity change of symptomatic IPH, CNRs of asymptomatic IPH exhibited a gradually descending trend on all contrast weighted images (P

Background and Purpose— Previous studies have reported that carotid atherosclerosis frequently can be seen in coronary artery disease (CAD) patients. This study sought to determine the prevalence of compositional features in subclinical carotid atherosclerosis by MRI in CAD patients. Methods— Ninety-six subjects with suspected CAD but free of neurological symptoms underwent coronary CT angiography and carotid MRI including 3-dimensional time-of-flight, T1-weighted, T2-weighted, and proton density-weighted sequences at 3 T within a 2-week interval. The coronary artery calcium score (CACS) and degree of stenosis were measured. Areas for carotid lumen, wall, total vessel, and percent wall volume (wall volume/total vessel volume) were measured. The prevalence of carotid calcification, lipid-rich necrotic core, intraplaque hemorrhage, and surface disruption in coronary stenosis and CACS categories were determined. Results— Carotid percent wall volume was correlated with CACS ( P =0.001). Both coronary stenosis and CACS were significantly associated with presence of carotid calcification (OR=5.79 for 1%–49% vs 0% stenosis; OR=10.23 for >50% vs 0% stenosis; OR=10.65 for CACS 1–399 vs CACS 0; and OR=20.28 for CACS >400 vs CACS 0; all P 50% vs 0% stenosis; OR=8.23 for CACS 1–399 vs CACS 0; and OR=11.87 for CACS >400 vs CACS 0; all P Conclusions— Carotid plaque burden and compositional features are significantly associated with CAD severity. The finding of high prevalence of lipid-rich necrotic core in patients with low-grade coronary stenosis and CACS suggests the need for early monitoring of carotid atherosclerosis in CAD patients.

The presence of IPH and/or FCR in the carotid atherosclerotic plaque indicates a high-risk lesion. The aim of this multicenter cross-sectional study was to establish the characteristics of lesions that may precede IPH and/or FCR. We further sought to construct a CAS that stratifies carotid disease severity.Three hundred forty-four individuals from 4 imaging centers with 16%-99% carotid stenosis by duplex sonography underwent carotid MR imaging. In approximately 60% of the study sample (training group), multivariate analysis was used to determine factors associated with IPH and FCR. Statistically significant parameters identified during multivariate analysis were used to construct CAS. CAS was then applied to the remaining arteries (40%, test group), and the accuracy of classification for determining the presence versus absence of IPH or, separately, FCR was determined by ROC analysis and calculation of the AUC.The maximum proportion of the arterial wall occupied by the LRNC was the strongest predictor of IPH (P.001) and FCR (P.001) during multivariate analysis of the training group. The subsequently derived CAS applied to the test group was an accurate classifier of IPH (AUC = 0.91) and FCR (AUC = 0.93). Compared with MRA stenosis, CAS was a stronger classifier of both IPH and FCR.LRNC quantification may be an effective complementary strategy to stenosis for classifying carotid atherosclerotic disease severity. CAS forms the foundation for a simple imaging-based risk-stratification system in the carotid artery to classify severity of atherosclerotic disease.

The purpose of this in vivo MRI study was to quantify changes in atherosclerotic plaque morphology prospectively and to identify factors that may alter the rate of progression in plaque burden. Sixty-eight asymptomatic subjects with >or=50% stenosis, underwent serial carotid MRI examinations over an 18-month period. Clinical risk factors for atherosclerosis, and medications were documented prospectively. The wall and total vessel areas, matched across time-points, were measured from cross-sectional images. The normalized wall index (NWI=wall area/total vessel area), as a marker of disease severity, was documented at baseline and at 18 months. Multiple regression analysis was used to correlate risk factors and morphological features of the plaque with the rate of progression/regression. On average, the wall area increased by 2.2% per year (P=0.001). Multiple regression analysis demonstrated that statin therapy (P=0.01) and a normalized wall index >0.64 (P=0.001) were associated with a significantly reduced rate of progression in mean wall area. All other documented risk factors were not significantly associated with changes in wall area. Findings from this study suggest that increased normalized wall index and the use of statin therapy are associated with reduced rates of plaque progression amongst individuals with advanced, asymptomatic carotid atherosclerosis.

"Vulnerable" plaques are atherosclerotic plaques that have a high likelihood to cause thrombotic complications, such as myocardial infarction or stroke. Plaques that tend to progress rapidly are also considered to be vulnerable. Besides luminal stenosis, plaque composition and morphology are key determinants of the likelihood that a plaque will cause cardiovascular events. Noninvasive magnetic resonance (MR) imaging has great potential to enable characterization of atherosclerotic plaque composition and morphology and thus to help assess plaque vulnerability. A classification for clinical, as well as pathologic, evaluation of vulnerable plaques was recently put forward in which five major and five minor criteria to define vulnerable plaques were proposed. The purpose of this review is to summarize the status of MR imaging with regard to depiction of the criteria that define vulnerable plaques by using existing MR techniques. The use of MR imaging in animal models and in human disease in various vascular beds, particularly the carotid arteries, is presented.

Background/Aims: As a major complication after thoracic radiotherapy, radiation-induced lung injury (RILI) has great impact on long term quality of life and could result in fatal respiratory insufficiency The present study was aimed to evaluate the effects of Myrtol standardized on RILI, and to investigate the underlying mechanism. Methods: A mouse model of radiation-induced lung injury was generated by using thoracic irradiation with a single dose of 16Gy. Mice were orally administrated with Myrtol (25 mg/kg/day) for 4 weeks after irradiation, while prednisone (5 mg/kg/day) was used as a positive control. After then, the body weight and lung coefficient were calculated. The severity of fibrosis was evaluated by observing pulmonary sections after radiation and collagen content in lung tissues was calculated following the hydroxyproline (HYP) assay. Pathological changes were observed in all the groups by using HE staining and Masson staining. The serum levels of TGF-β1, TNF-α, IL-1β, IL-6, and PGE2 were also measured with an ELISA assay. Western blot assay was used to measure the impact of Myrtol on AKT and its downstream signaling pathway, including MMP-2 and MMP-9. The levels of Vimentin and α-SMA were evaluated with an immunofluorescence assay. Results: Treatment with Myrtol standardized, but not prednisone, reduced lung coefficient and collagen deposition in lung tissues, while attenuated histological damages induced by irradiation. Myrtol standardized also reduced the production of MDA, while increased the level of SOD. It was also observed that Myrtol standardized inhibited TGF-β1 and a series of pro-inflammatory cytokines including TNF-α, IL-1β, IL-6, PGE2. While in prednisone group, even though the early pneumonitis was ameliorated, the collagen disposition remained unchanged in latter times. Immunofluorescence analysis also revealed elevation of vimentin and α-SMA in the alveoli after a single dose of 16Gy. Conclusion: The present results suggest Myrtol standardized as an effective agent for attenuating the lung injury induced by irradiation.

Changes in plaque tissue components such as lipid-rich necrotic core (LRNC) and fibrous tissue with long-term statin treatment or discontinuation have not been studied.LRNC and fibrous tissue by magnetic resonance imaging were evaluated in subjects who continued and discontinued statin therapy for 2 years after a prospective study.The Rosuvastatin Evaluation of Atherosclerotic Chinese Patients study in 32 lipid treatment naïve subjects showed a significant reduction in LRNC during 24 months of rosuvastatin therapy. After Rosuvastatin Evaluation of Atherosclerotic Chinese Patients was completed, 15 subjects continued taking statins and 17 discontinued despite receiving an instruction to continue statin therapy. LRNC and fibrous tissue were compared between 24 and 48 months within each group and between the 2 groups.At 48 months, LRNC volume and composition decreased significantly compared with that at 24 months in the statin-continued group (101 ± 76 vs 76 ± 65 mm(3); P = .001 and 17.3 ± 11.9% vs 12.6 ± 7.6%; P = .04), whereas fibrous tissue increased significantly in both volume (337 ± 160 vs 357 ± 169 mm(3); P .001) and composition (76.3 ± 10.5% vs 83.1 ± 10.1%, P = .002). Such changes were not seen in subjects who discontinued statin. Furthermore, the changes in LRNC volume and composition and fibrous tissue composition from 24 to 48 months were significantly different between the statin-continued and -discontinued groups (-25 ± 18 vs 9 ± 14 mm(3); P .001) and (-4.6 ± 8.2% vs 1.3 ± 2.8%; P = .009) and (6.9 ± 6.8% vs 1.3 ± 5.4%, P = .018).Continued statin therapy leads to continued decrease in LRNC and increase in fibrous tissue, which indicates improved plaque stability and supports long-term statin therapy.

The role of Toll-like receptor-2 (TLR2) in radio-resistance remained largely unknown. TLR2 knockout (TLR2−/−) mice received radiation of 6.5 Gy and then were studied. We found that radiation resulted in more severe mortality and morbidity rates in TLR2−/− mice. The cause of death in TLR2−/− mice may be severe and persistent bone marrow cell loss. Injection of the TLR2 agonist Pam3CSK4 into wild type (WT) mice induced radio-resistance. Myd88−/− mice were more susceptible to radiation. In conclusion, our data indicate that, similar to TLR4, TLR2 plays a critical role in radio-resistance.

The value of noninvasive assessment of carotid plaque composition in identifying patients with high coronary risk remains elusive. We sought to determine whether and which carotid plaque components are associated with prior coronary events independent of traditional risk factors and plaque burden. Asymptomatic subjects with 50-79 % carotid stenosis by ultrasound were imaged with a multi-contrast carotid MRI protocol at 1.5 T. The independent associations between plaque components (fibrous tissue, calcification, lipid-rich necrotic core [LRNC] and intraplaque hemorrhage [IPH]) and prior coronary events, including myocardial infarction and coronary revascularization, were evaluated by controlling for traditional risk factors and plaque burden metrics. A total of 159 subjects (69.7 ± 9.0 years, 84 % males) were included. Prior coronary events were documented in 66 (42 %) subjects, and were associated with a larger carotid plaque burden consisting of more LRNC and calcification. Additionally, a higher prevalence of IPH was observed in subjects with prior coronary events (32 % vs. 15 %, p = 0.019). In multivariate analysis, the percent wall volume was an independent discriminator among plaque burden metrics after accounting for traditional risk factors (odds ratio per 1-SD increase: 1.7 [1.2, 2.6]); the presence of IPH remained as a significant discriminator after accounting for traditional risk factors and percent wall volume (odds ratio: 2.9 [1.1, 7.6]) while other compositional metrics did not. IPH in the carotid artery was independently associated with prior coronary events. IPH imaging may provide incremental information on patients’ coronary risk beyond traditional risk factors and carotid plaque burden assessment.

To retrospectively determine if in vivo magnetic resonance (MR) imaging can simultaneously depict differences between symptomatic and asymptomatic carotid atherosclerotic plaque.Institutional review board approval and informed consent were obtained for this HIPAA-compliant study. Twenty-three patients (21 men, two women; mean age, 66.1 years +/- 11.0 [standard deviation]) with unilateral symptomatic carotid disease underwent 1.5-T time-of-flight MR angiography and 1.5-T T1-, intermediate-, and T2-weighted MR imaging. Both carotid arteries were reviewed. One observer recorded quantitative and morphologic information, which included measurement of the area of the lumen, artery wall, and main plaque components; fibrous cap status (thick, thin, or ruptured); American Heart Association (AHA) lesion type (types I-VIII); and location (juxtaluminal vs intraplaque) and type of hemorrhage. Plaques associated with neurologic symptoms and asymptomatic plaques were compared with Wilcoxon signed rank and McNemar tests.Compared with asymptomatic plaques, symptomatic plaques had a higher incidence of fibrous cap rupture (P = .007), juxtaluminal hemorrhage or thrombus (P = .039), type I hemorrhage (P = .021), and complicated AHA type VI lesions (P = .004) and a lower incidence of uncomplicated AHA type IV and V lesions (P = .005). Symptomatic plaques also had larger hemorrhage (P = .003) and loose matrix (P = .014) areas and a smaller lumen area (P = .008). No significant differences between symptomatic and asymptomatic plaques were found for quantitative measurements of the lipid-rich necrotic core, calcification, and the vessel wall or for the occurrence of intraplaque hemorrhage or type II hemorrhage.This study revealed significant differences between symptomatic and asymptomatic plaques in the same patient.

Purpose To test the hypothesis that intra- and interreader reproducibility for measuring the lipid-rich necrotic core (LR-NC) size is significantly improved with gadolinium (Gd) contrast-enhanced magnetic resonance imaging (CEMRI) compared to non-CEMRI. Materials and Methods Thirty-seven individuals with >50% carotid artery stenosis underwent carotid MRI at 1.5T (pre- and postcontrast T1-weighted (T1W), T2-weighted (T2W), proton density-weighted (PDW), and three-dimensional time-of-flight (TOF) sequences). Two independent readers measured the mean area of the LR-NC from the precontrast images only, followed by a second measurement using the additional postcontrast images. One reader repeated the measurements after an interval of five months. Intra- and interreader reproducibility was analyzed by means of the intraclass correlation coefficient (ICC), coefficient of variation (CV), and standard deviation (SD). Results The CV decreased from 33.7% to 8.8% for intrareader measurements of the LR-NC, and from 33.5% to 17.6% for interreader measurements. The SD was significantly smaller with CEMRI than with non-CEMRI (P = 0.003 and P = 0.006, respectively). The ICC increased from 0.94 to 0.99 and from 0.85 to 0.93 for the intra- and interreader measurements, respectively. Conclusion Reader reproducibility for in vivo MRI quantification of LR-NC size is significantly improved by the addition of Gd contrast in individuals with >50% carotid stenosis. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc.

Background— Previous studies with contrast-enhanced magnetic resonance imaging (CEMRI) have shown that the fibrous cap (FC) in atherosclerotic carotid plaques enhances with gadolinium-based contrast agents. Conversely, the lipid-rich necrotic core (LR-NC), lacking both vasculature and matrix, shows no or only slight enhancement. The goal of this study was to assess whether CEMRI can be used to accurately measure the dimensions of the intact FC and LR-NC. Methods and Results— Twenty-one patients scheduled for carotid endarterectomy were imaged with a 1.5-T scanner. Precontrast images and CEMRI were obtained. One hundred eight locations with an intact FC were matched between MRI and the excised histology specimens. Quantitative measurements of FC length along the lumen circumference, FC area, and LR-NC area were collected from CEMRI images and histology sections. Blinded comparison of corresponding MR images and histology slices showed moderate to good correlation for length ( r =0.73, P r =0.80, P r =0.87, P Conclusions— In vivo high-resolution CEMRI is capable of quantitatively measuring the dimensions of the intact FC and LR-NC. These new parameters may be useful to evaluate plaque vulnerability and provide continuous variables for characterizing the intact FC and LR-NC in progression and regression studies.

High-resolution imaging techniques that permit serial, in vivo examination of the atherosclerotic plaque are needed to better understand the mechanisms involved in the progression of stable, early lesions into high-risk plaques in humans. Such an imaging tool would serve as a bridge between what is learned in the laboratory and the clinical setting. Furthermore, it would permit direct assessment of the efficacy of phamacological interventions.Magnetic resonance imaging (MRI) is ideally suited for serial examination of the diseased arterial wall. Studies have shown that MRI is capable of measuring plaque burden, identifying fibrous cap characteristics and lesion types using American Heart Association (AHA) criteria, and quantifying neovasculature within the plaque. Case-control studies have shown an association between thin/ruptured fibrous caps, as identified by MRI, and recent transient ischemic attack (TIA) and stroke, and have shown that prolonged intensive lipid-lowering therapy is associated with decreased plaque lipid content.Thus, MRI is a promising tool for direct, serial assessment of carotid atherosclerosis in vivo. This article will briefly review our previously published work validating the technique.

Purpose To evaluate the in vivo accuracy of a multisequence MRI technique for prospectively identifying one feature of the vulnerable plaque—an unstable fibrous cap—in human carotid atherosclerosis. Materials and Methods The carotid arteries of 18 endarterectomy patients were preoperatively imaged in a 1.5T scanner using a multisequence protocol that generated four contrast weightings (3D time of flight (ToF), T1, proton density (PD), and T2) at each slice location. With the use of previously published MR criteria, the images of the vessel wall were first examined for evidence of an unstable fibrous cap. The imaging findings were then correlated with the histology from the surgical specimens. Results A blinded review of the MR findings with the histologic state of the fibrous cap revealed that 1) assessing the preoperative appearance of the fibrous cap has a high test sensitivity (0.81) and specificity (0.90) for identifying an unstable cap in vivo; and 2) the availability of different contrast weightings facilitated image interpretation when intimal calcifications or flow artifacts obscured the lumen surface. Conclusion Multisequence MRI can accurately characterize the in vivo state of the fibrous cap. This finding supports the use of these noninvasive techniques to prospectively identify vulnerable plaques. J. Magn. Reson. Imaging 2003;17:410–420. Published 2003 Wiley-Liss, Inc.

High spatial resolution magnetic resonance imaging (MRI) is one of the most promising modalities for visualizing the carotid atherosclerotic plaque. MR allows direct visualization of the diseased vessel wall, is capable of characterizing plaque morphology, and can potentially monitor progression of the disease. Though ultrasound and angiography have been the principal methods for determining the severity of carotid atherosclerosis and the need for endarterectomy, these methods only measure percentage of vessel stenosis. There is strong evidence that this is not the best indicator for assessing clinical risk. Improved imaging techniques are therefore needed to reliably identify the high-risk plaques that lead to cerebrovascular events. This article focuses on the current state-of-the-art in MR carotid atherosclerotic plaque imaging to evaluate plaque morphology and composition.

Purpose To determine if a gadolinium-based contrast agent provides additional information for characterization of human plaque tissues, particularly neovasculature. Although high-resolution magnetic resonance imaging (MRI) has been used to identify plaque constituents in advanced atherosclerosis, some constituents, such as neovascularized tissue, defy detection. Materials and Methods Non-contrast-enhanced carotid artery images from 18 patients scheduled for carotid endarterectomy and two normal volunteers were used to identify regions of fibrous tissue, necrotic core, or calcification, using established criteria. Then, the percent change in T1-weighted images after contrast enhancement was calculated for each region. Results There were statistically significant differences in mean intensity change between tissues, with the largest increase for fibrous tissue (79.5%) and the smallest for necrotic core (28.6%). Additionally, histological analysis showed that a subset of fibrous regions rich in plaque neovascularization could be identified using a threshold of 80% enhancement (sensitivity = 76%, specificity = 79%). Conclusion: The ability of contrast-enhanced MRI to identify neovascularization and potentially improve differentiation of necrotic core from fibrous tissue further establishes MRI as a viable tool for in vivo study of atherosclerotic plaque. J. Magn. Reson. Imaging 2002;15:62–67. Published 2002 Wiley-Liss, Inc.

Background the bone marrow and the intestine are the major sites of ionizing radiation (IR)-induced injury. Our previous study demonstrated that CpG-oligodeoxynucleotide (ODN) treatment mitigated IR-induced bone marrow injury, but its effect on the intestine is not known. In this study, we sought to determine if CpG-ODN have protective effect on IR-induced intestine injury, and if so, to determine the mechanism of its effect. Methods and Findings Mice were treated with CpG-ODN after IR. The body weight and survival were daily monitored for 30 days consecutively after exposure. The number of surviving intestinal crypt was assessed by the microcolony survival assay. The number and the distribution of proliferating cell in crypt were evaluated by TUNEL assay and BrdU assay. The expression of Bcl-2, Bax and caspase-3 in crypt were analyzed by Immunohistochemistry assay. The findings showed that the treatment for irradiated mice with CpG-ODN diminished body weight loss, improved 30 days survival, enhanced intestinal crypts survival and maintained proliferating cell population and regeneration in crypt. The reason might involve that CpG-ODN up-regulated the expression of Bcl-2 protein and down-regulated the expression of Bax protein and caspase-3 protein. Conclusion CpG-ODN was effective in protection of IR-induced intestine injury by enhancing intestinal crypts survival and maintaining proliferating cell population and regeneration in crypt. The mechanism might be that CpG-ODN inhibits proliferating cell apoptosis through regulating the expression of apoptosis-related protein, such as Bax, Bcl-2 and caspase-3.

The aim of the present study was to evaluate the association between coronary calcification and carotid atherosclerosis. Briefly, 123 patients with suspected coronary artery disease were recruited. The coronary artery calcium score (CACS) was measured and multi‑contrast carotid magnetic resonance imaging (MRI) was performed. Parameters of the carotid morphological measurements were determined and the presence or absence of carotid plaque tissue compositions was recorded for each subject, as well as plaque surface disruption. Two reviewers blind to CACS status interpreted the MRIs. All the subjects were divided into two groups, high‑ and low‑CACS and the carotid morphological measurements in the CACS groups and categories were compared using independent t‑tests and one way ANOVA, respectively. CACS was found to exhibit a moderate correlation with carotid wall area (WA; r=0.521) and mean wall thickness (MWT; r=0.556) and a weak correlation with total vessel area (TVA; r=0.215) and normalized wall index (r=0.377). No significant correlation between CACS and carotid lumen area was identified. Compared with low‑CACS, the high‑CACS group revealed increased carotid WA, TVA and MWT. In the entire cohort, carotid plaque burden revealed an increasing trend with an increasing CACS. CACS and presence of carotid calcification and lipid‑rich necrotic core (LRNC) demonstrated a significant correlation. No significant correlation was observed between CACS with carotid intraplaque hemorrhage (IPH) and surface disruption. CACS was found to moderately correlate with carotid calcification and LRNC volume and weakly correlate with carotid IPH volume. Results of the present study indicated that CACS significantly correlates with carotid atherosclerotic plaque burden and the presence of tissue compositions.

Background and Purpose— To determine associations between stenosis, measures of plaque burden, and compositional features of carotid atherosclerosis, including high-risk features of intraplaque hemorrhage (IPH) and surface disruption. Methods— Institutional Review Board approval and informed consent for all participants were obtained before study initiation. Patients with either carotid stenosis >50% by duplex ultrasound or suspected coronary artery disease underwent multi-contrast carotid MRI at 3.0 T. For each artery, stenosis, percent wall volume (PWV=100%×wall volume/total vessel volume), and mean wall thickness (MWT) were measured. Presence or absence of a lipid-rich necrotic core, calcification, IPH, and surface disruption were recorded. Results— One hundred eighty-one patients were included in the final analysis. The area under the curve (AUC) calculated from receiver-operating-characteristics analysis found the presence of IPH was similarly classified by stenosis (AUC=0.82), PWV (AUC=0.88), and MWT (AUC=0.88). Notably, IPH was present in the lowest category of each parameter. Prevalence of IPH in arteries with 0% stenosis was 4.4%. In arteries with PWV Conclusions— Measures of plaque burden do not substantially improve disease assessment compared to stenosis. The finding of IPH in all categories of stenosis and plaque burden suggests that direct characterization of plaque composition and surface status is necessary to fully discriminate disease severity.

Inflammation plays an important role in progression and rupture of atherosclerotic plaque. Dynamic contrast-enhanced MRI has been proposed as a tool to evaluate inflammation in vivo by measuring the transfer constant and partial plasma volume, which are influenced by inflammation. This study sought to demonstrate the ability of dynamic contrast-enhanced MRI to provide localized measurements of transfer constant and partial plasma volume within plaque regions of different compositions. In order to do that, a highly automatic procedure for localized measurement of dynamic contrast-enhanced MRI parameters was developed. In 47 subjects, the average transfer constant and partial plasma volume were highest in loose matrix and fibrous tissue and substantially lower in intraplaque hemorrhage, lipid rich/necrotic core, and calcification. In addition, except for hemorrhage and calcification, statistically significant differences of transfer constant and partial plasma volume were observed for any pair of these components. This suggests that transfer constant and partial plasma volume could be helpful to differentiate different plaque components and that dynamic contrast-enhanced MRI has the potential to assess inflammatory burden in specific regions.

Multicontrast, high-resolution carotid magnetic resonance imaging (MRI) has been validated with histology to quantify atherosclerotic plaque morphology and composition. For evaluating the lipid-rich necrotic core (LRNC) and fibrous cap, both of which are key elements in determining plaque stability, the combined pre- and postcontrast T1-weighted (T1W) sequences have been recently shown to have a higher reproducibility than other contrast weightings. In this study, we sought to determine whether contrast weightings beyond T1W (pre- and postcontrast) are necessary for comprehensive, quantitative, carotid plaque interpretation.Our HIPAA compliant study protocol was approved by the IRB and all participants gave written, informed consent. Sixty-five participants with carotid stenosis50% detected by ultrasound underwent carotid MRI with a standard multicontrast protocol (time-of-flight [TOF], T1W, contrast-enhanced [CE]-T1W, proton density [PD], and T2W). For each subject, images were partitioned into 3 combinations of contrast weightings (CW): (1) 2CW: T1W and CE-T1W; (2) 3CW: T1W, CE-T1W, and TOF; and (3) 5CW: T1W, CE-T1W, TOF, PD, and T2W. Each CW set was interpreted by 2 reviewers, blinded to results of each of the other CW combinations, via consensus opinion. Wall, lumen, and total vessel volumes, along with mean wall thickness were recorded. The presence or absence of calcification, LRNC, intraplaque hemorrhage (IPH), and surface disruption was also documented.Compared with 5CW, there was strong agreement in the parameters of plaque morphology for 2CW (intraclass correlation coefficient, 0.96-0.99) and 3CW (intraclass correlation coefficient, 0.97-1.00). Agreement with 5CW for the detection of plaque composition was stronger for 3CW compared with 2CW: Cohen's kappa, 0.59 versus 0.42 for calcification; 0.75 versus 0.47 for LRNC; 0.91 versus 0.88 for IPH; and 0.74 versus 0.34 for surface disruption. Using 5CW as the reference standard during receive-operating-characteristics analysis, 3CW compared with 2CW showed a larger area-under-the-curve for classifying the presence or absence of calcification (0.78 vs. 0.69), LRNC (0.98 vs. 0.69), and surface disruption (0.87 vs. 0.65), and similar area-under-the-curve in classifying IPH (0.96 vs. 0.94).Comprehensive, quantitative carotid plaque interpretation can be performed with T1W, CE-T1W, and TOF sequences. Elimination of PD and T2W sequences from the carotid MRI protocol may result in a substantial reduction in scan time. The ability to perform plaque interpretation on images acquired within a clinically acceptable scan time may broaden the research utility of carotid MRI and increase translatability to clinical applications.

Objectives Via magnetic resonance imaging (MRI), we sought to determine the prevalence of atherosclerotic American Heart Association type VI lesions (AHA-LT6) (lesions with luminal surface defect, hemorrhage/thrombus, or calcified nodule) in carotid arteries that represented all categories of stenosis as measured by duplex ultrasound. Background Arterial stenosis alone has been shown to be a poor predictor of cardiovascular events. Autopsy studies suggest that features associated with AHA-LT6 lesions, rather than the degree of luminal narrowing, characterize the high-risk plaque. Methods A total of 192 subjects underwent bilateral carotid artery magnetic resonance imaging (MRI) scans at 1.5T after evaluation with ultrasound to determine stenosis. After excluding arteries with a previous endarterectomy, poor image quality, or missing ultrasound data, there were 175 patients with 260 arteries available for analysis. The AHA lesion type was determined by the consensus opinion of 2 experienced carotid MRI reviewers. Results In total, 96 of 260 (37.0%) arteries had ≥1 location with AHA-LT6. Of the arteries with AHA-LT6, 84.4% had hemorrhage, 45.8% had a ruptured fibrous cap, and 14.6% showed other type of complications. Prevalence of AHA-LT6 was an increasing sequence of 8.1% in the 37 arteries with 1% to 15% stenosis, 21.7% in the 60 arteries with 16% to 49% stenosis, 36.8% in the 114 arteries with 50% to 79% stenosis, and 77.6% in the 49 arteries with 80% to 99% stenosis. Conclusions Complicated AHA-LT6 are frequently found in arteries with ≤50% stenosis. These findings indicate that complex lesions develop in a substantial number of arteries in the absence of high-grade stenosis. Ongoing prospective studies will determine the predictive value of vulnerable plaque features, as visualized by MRI, for risk of subsequent ischemic events.

Magnetic resonance imaging (MRI) of the arterial wall has emerged as a viable technology for characterizing atherosclerotic lesions in vivo, especially within carotid arteries and other large vessels. This capability has facilitated the use of carotid MRI in clinical trials to evaluate therapeutic effects on atherosclerotic lesions themselves. MRI is specifically able to characterize three important aspects of the lesion: size, composition and biological activity. Lesion size, expressed as a total wall volume, may be more sensitive than maximal vessel narrowing (stenosis) as a measure of therapeutic effects, as it reflects changes along the entire length of the lesion and accounts for vessel remodeling. Lesion composition (e.g. lipid, fibrous and calcified content) may reflect therapeutic effects that do not alter lesion size or stenosis, but cause a transition from a vulnerable plaque composition to a more stable one. Biological activity, most notably inflammation, is an emerging target for imaging that is thought to destabilize plaque and which may be a systemic marker of vulnerability. The ability of MRI to characterize each of these features in carotid atherosclerotic lesions gives it the potential, under certain circumstances, to replace traditional trials involving large numbers of subjects and hard end-points--heart attacks and strokes--with smaller, shorter trials involving imaging end-points. In this review, the state of the art in MRI of atherosclerosis is presented in terms of hardware, image acquisition protocols and post-processing. Also, the results of validation studies for measuring lesion size, composition and inflammation will be summarized. Finally, the status of several clinical trials involving MRI of atherosclerosis will be reviewed.

Background and Purpose— MRI is able to quantify carotid plaque size and composition with good accuracy and reproducibility and provides an opportunity to prospectively examine the relationship between plaque features and subsequent cerebrovascular events. We tested the hypothesis that the characteristics of carotid plaque, as assessed by MRI, are possible predictors of future ipsilateral cerebrovascular events. Methods— A total of 154 consecutive subjects who initially had an asymptomatic 50% to 79% carotid stenosis by ultrasound with ≥12 months of follow-up were included in this study. Multicontrast-weighted carotid MRIs were performed at baseline, and participants were followed clinically every 3 months to identify symptoms of cerebrovascular events. Results— Over a mean follow-up period of 38.2 months, 12 carotid cerebrovascular events occurred ipsilateral to the index carotid artery. Cox regression analysis demonstrated a significant association between baseline MRI identification of the following plaque characteristics and subsequent symptoms during follow-up: presence of a thin or ruptured fibrous cap (hazard ratio, 17.0; P ≤0.001), intraplaque hemorrhage (hazard ratio, 5.2; P =0.005), larger mean intraplaque hemorrhage area (hazard ratio for 10 mm 2 increase, 2.6; P =0.006), larger maximum %lipid-rich/necrotic core (hazard ratio for 10% increase, 1.6; P =0.004), and larger maximum wall thickness (hazard ratio for a 1-mm increase, 1.6; P =0.008). Conclusions— Among patients who initially had an asymptomatic 50% to 79% carotid stenosis, arteries with thinned or ruptured fibrous caps, intraplaque hemorrhage, larger maximum %lipid-rich/necrotic cores, and larger maximum wall thickness by MRI were associated with the occurrence of subsequent cerebrovascular events. Findings from this prospective study provide a basis for larger multicenter studies to assess the risk of plaque features for subsequent ischemic events.

A 62-year-old man presented to the emergency department with a chief complaint of severe headache and decreased vision in his left eye. Initial physical examination demonstrated a new-onset left homonymous hemianopsia, which warranted a stroke workup. The patient’s head CT was significant for a 2.3×3.7-cm acute hemorrhage in the right posterior parietal and occipital lobes. Conventional angiography was performed and interpreted as >90% stenosis of both internal carotid arteries without ulceration. The remainder of the work-up, including …

Purpose To test the image quality (ImQ) and interscan coverage of MRI for measuring carotid atherosclerosis across multiple centers. Materials and Methods Thirty-nine subjects from five clinical sites (site 1: n = 11; site 2: n = 16; site 3: n = 2; site 4: n = 3; site 5: n = 7) were imaged on GE 1.5T scanners using a standardized carotid imaging protocol with five weightings (T1, proton density (PD), T2, time-of-flight (TOF), and contrast-enhanced (CE) T1). MR technologists from the five sites received comprehensive protocol training. A maximum coverage of 24 mm (12 slices) was designed for each of four scans (baseline and at four, eight, and 13 weeks). The adequacy of coverage was calculated as the percentage of arteries with at least six slices matched across all four scans. ImQ was evaluated using an established five-point scale for each image. ImQ ≥ 3 was considered acceptable for image analysis. Results Across five sites, the mean ImQ was 3.4–4.2 for T1W, 3.6–4.4 for CE-T1W, 3.4–4.2 for PDW, 3.3–4.2 for T2W, and 3.4–4.0 for TOF. The mean ImQ per site was 3.5–4.2. All sites generated at least six-slice coverage (mean = 8.0–9.1) for all index carotid arteries. Conclusion The ImQ and coverage values were comparable among clinical sites using a standardized carotid imaging protocol. With comprehensive protocol training, carotid MRI is technically feasible for use in multicenter studies. J. Magn. Reson. Imaging 2005;21:809–817. © 2005 Wiley-Liss, Inc.