Dynamic Contrast-enhanced MR Imaging of Carotid Atherosclerotic Plaque: Model Selection, Reproducibility, and Validation.

Purpose: compare four known pharmacokinetic models for their ability to describe dynamic contrast material-enhanced magnetic resonance (MR) imaging of carotid atherosclerotic plaques, to determine reproducibility, and to validate the results with histologic findings. Materials and Methods: The study was approved by the institutional medical ethics committee. Written informed consent was obtained from all patients. Forty-five patients with 30%-99% carotid stenosis underwent dynamic contrast-enhanced MR imaging. Plaque enhancement was measured at 16 time points at approximately 25-second image intervals by using a gadolinium-based contrast material. Pharmacokinetic parameters (volume transfer constant, Ktrans; extracellular extravascular volume fraction, v e; and blood plasma fraction, v p) were determined by fitting a two-compartment model to plaque and blood gadolinium concentration curves. The relative fit errors and parameter uncertainties were determined to find the most suitable model. Sixteen patients underwent imaging twice to determine reproducibility. Carotid endarterectomy specimens from 16 patients who were scheduled for surgery were collected for histologic validation. Parameter uncertainties were compared with the Wilcoxon signed rank test. Reproducibility was assessed by using the coefficient of variation. Correlation with histologic findings was evaluated with the Pearson correlation coefficient. Results: The mean relative fit uncertainty (+/- standard error) for Ktrans was 10% +/- 1 with the Patlak model, which was significantly lower than that with the Tofts (20% +/- 1), extended Tofts (33% +/- 3), and extended graphical (29% +/- 3) models (P <.001). The relative uncertainty for v p was 20% 6 2 with the Patlak model and was significantly higher with the extended Tofts (46% +/- 9) and extended graphical (35% +/- 5) models (P <.001). The reproducibility (coefficient of variation) for the Patlak model was 16% for Ktrans and 26% for v p. Significant positive correlations were found between Ktrans and the endothelial microvessel content determined on histologic slices (Pearson r = 0.72, P = .005). Conclusion: The Patlak model is most suited for describing carotid plaque enhancement. Correlation with histologic findings validated Ktrans as an indicator of plaque microvasculature, and the reproducibility of Ktrans was good. (C)RSNA, 201

NO-Donating Aspirin and Aspirin Partially Inhibit Age-Related Atherosclerosis but Not Radiation-Induced Atherosclerosis in ApoE Null Mice

BACKGROUND: We previously showed that irradiation to the carotid arteries of ApoE(-/-) mice accelerated the development of macrophage-rich, inflammatory atherosclerotic lesions, prone to intra-plaque hemorrhage. In this study we investigated the potential of anti-inflammatory and anti-coagulant intervention strategies to inhibit age-related and radiation-induced atherosclerosis. METHODOLOGY/PRINCIPAL FINDINGS: ApoE(-/-) mice were given 0 or 14 Gy to the neck and the carotid arteries and aortic arches were harvested at 4 or 30 weeks after irradiation. Nitric oxide releasing aspirin (NCX 4016, 60 mg/kg/day) or aspirin (ASA, 30 or 300 mg/kg/day) were given continuously in the chow. High dose ASA effectively blocked platelet aggregation, while the low dose ASA or NCX 4016 had no significant effect on platelet aggregation. High dose ASA, but not NCX 4016, inhibited endothelial cell expression of VCAM-1 and thrombomodulin in the carotid arteries at 4 weeks after irradiation; eNOS and ICAM-1 levels were unchanged. After 30 weeks of follow-up, NCX 4016 significantly reduced the total number of lesions and the number of initial macrophage-rich lesions in the carotid arteries of unirradiated mice, but these effects were not seen in the brachiocephalic artery of the aortic arch (BCA). In contrast, high dose ASA lead to a decrease in the number of initial lesions in the BCA, but not in the carotid artery. Both high dose ASA and NCX 4016 reduced the collagen content of advanced lesions and increased the total plaque burden in the BCA of unirradiated mice. At 30 weeks after irradiation, neither NCX 4016 nor ASA significantly influenced the number or distribution of lesions, but high dose ASA lead to formation of collagen-rich "stable" advanced lesions in carotid arteries. The total plaque area of the irradiated BCA was increased after ASA, but the plaque burden was very low compared with the carotid artery. CONCLUSIONS/SIGNIFICANCE: The development and characteristics of radiation-induced atherosclerosis varied between different arteries but could not be circumvented by anti-inflammatory and anti-coagulant therapies. This implicates other underlying mechanistic pathways compared to age-related atherosclerosis

Leukocyte Counts, Myeloperoxidase, and Pregnancy-Associated Plasma Protein A as Biomarkers for Cardiovascular Disease: Towards a Multi-Biomarker Approach

We evaluated leukocyte counts and levels of CRP, fibrinogen, MPO, and PAPP-A in patients with stable and unstable angina pectoris, acute myocardial infarction, and healthy controls. All biomarkers were analyzed again after 6 months. Leukocyte counts and concentrations of fibrinogen, CRP, MPO, and PAPP-A were significantly increased in patients with acute myocardial infarction. Leukocyte counts and concentrations of MPO were significantly increased in patients with unstable angina pectoris compared with controls. After 6 months, leukocyte counts and MPO concentrations were still increased in patients with acute myocardial infarction when compared to controls. Discriminant analysis showed that leukocyte counts, MPO, and PAPP-A concentrations classified study group designation for acute coronary events correctly in 83% of the cases. In conclusion, combined assessment of leukocyte counts, MPO, and PAPP-A was able to correctly classify acute coronary events, suggesting that this could be a promising panel for a multibiomarker approach to assess cardiovascular risk

Changing the culture of assessment: the dominance of the summative assessment paradigm

Background Despite growing evidence of the benefits of including assessment for learning strategies within programmes of assessment, practical implementation of these approaches is often problematical. Organisational culture change is often hindered by personal and collective beliefs which encourage adherence to the existing organisational paradigm. We aimed to explore how these beliefs influenced proposals to redesign a summative assessment culture in order to improve students’ use of assessment-related feedback. Methods Using the principles of participatory design, a mixed group comprising medical students, clinical teachers and senior faculty members was challenged to develop radical solutions to improve the use of post-assessment feedback. Follow-up interviews were conducted with individual members of the group to explore their personal beliefs about the proposed redesign. Data were analysed using a socio-cultural lens. Results Proposed changes were dominated by a shared belief in the primacy of the summative assessment paradigm, which prevented radical redesign solutions from being accepted by group members. Participants’ prior assessment experiences strongly influenced proposals for change. As participants had largely only experienced a summative assessment culture, they found it difficult to conceptualise radical change in the assessment culture. Although all group members participated, students were less successful at persuading the group to adopt their ideas. Faculty members and clinical teachers often used indirect techniques to close down discussions. The strength of individual beliefs became more apparent in the follow-up interviews. Conclusions Naïve epistemologies and prior personal experiences were influential in the assessment redesign but were usually not expressed explicitly in a group setting, perhaps because of cultural conventions of politeness. In order to successfully implement a change in assessment culture, firmly-held intuitive beliefs about summative assessment will need to be clearly understood as a first step

Factors influencing students’ receptivity to formative feedback emerging from different assessment cultures

Introduction Feedback after assessment is essential to support the development of optimal performance, but often fails to reach its potential. Although different assessment cultures have been proposed, the impact of these cultures on students’ receptivity to feedback is unclear. This study aimed to explore factors which aid or hinder receptivity to feedback. Methods Using a constructivist grounded theory approach, the authors conducted six focus groups in three medical schools, in three separate countries, with different institutional approaches to assessment, ranging from a traditional summative assessment structure to a fully implemented programmatic assessment system. The authors analyzed data iteratively, then identified and clarified key themes. Results Helpful and counterproductive elements were identified within each school’s assessment system. Four principal themes emerged. Receptivity to feedback was enhanced by assessment cultures which promoted students’ agency, by the provision of authentic and relevant assessment, and by appropriate scaffolding to aid the interpretation of feedback. Provision of grades and comparative ranking provided a helpful external reference but appeared to hinder the promotion of excellence. Conclusions This study has identified important factors emerging from different assessment cultures which, if addressed by programme designers, could enhance the learning potential of feedback following assessments. Students should be enabled to have greater control over assessment and feedback processes, which should be as authentic as possible. Effective long-term mentoring facilitates this process. The trend of curriculum change towards constructivism should now be mirrored in the assessment processes in order to enhance receptivity to feedback