Contrast-enhanced micro-CT imaging in murine carotid arteries : a new protocol for computing wall shear stress

Background: Wall shear stress (WSS) is involved in the pathophysiology of atherosclerosis. The correlation between WSS and atherosclerosis can be investigated over time using a WSS-manipulated atherosclerotic mouse model. To determine WSS in vivo, detailed 3D geometry of the vessel network is required. However, a protocol to reconstruct 3D murine vasculature using this animal model is lacking. In this project, we evaluated the adequacy of eXIA 160, a small animal contrast agent, for assessing murine vascular network on micro-CT. Also, a protocol was established for vessel geometry segmentation and WSS analysis. Methods: A tapering cast was placed around the right common carotid artery (RCCA) of ApoE(-/-) mice (n = 8). Contrast-enhanced micro-CT was performed using eXIA 160. An innovative local threshold-based segmentation procedure was implemented to reconstruct 3D geometry of the RCCA. The reconstructed RCCA was compared to the vessel geometry using a global threshold-based segmentation method. Computational fluid dynamics was applied to compute the velocity field and WSS distribution along the RCCA. Results: eXIA 160-enhanced micro-CT allowed clear visualization and assessment of the RCCA in all eight animals. No adverse biological effects were observed from the use of eXIA 160. Segmentation using local threshold values generated more accurate RCCA geometry than the global threshold-based approach. Mouse-specific velocity data and the RCCA geometry generated 3D WSS maps with high resolution, enabling quantitative analysis of WSS. In all animals, we observed low WSS upstream of the cast. Downstream of the cast, asymmetric WSS patterns were revealed with variation in size and location between animals. Conclusions: eXIA 160 provided good contrast to reconstruct 3D vessel geometry and determine WSS patterns in the RCCA of the atherosclerotic mouse model. We established a novel local threshold-based segmentation protocol for RCCA reconstruction and WSS computation. The observed differences between animals indicate the necessity to use mouse-specific data for WSS analysis. For our future work, our protocol makes it possible to study in vivo WSS longitudinally over a growing plaque

The effectiveness of metacognitive therapy in comparison to exposure and response prevention for obsessive-compulsive disorder:A randomized controlled trial

Background: The recommended psychological treatment of choice for obsessive-compulsive disorder (OCD) is exposure with response prevention (ERP). Although this treatment is quite effective, recovery rates are modest and attrition rate is relatively high. Also, ERP treatment requires amounts of therapist time. A possible way to improve OCD treatment is by taking into account key cognitive processes involved in the development and maintenance of the disorder. The metacognitive model is such an account and pilot findings suggest that the associated metacognitive therapy (MCT) might be an effective treatment for OCD. Methods: In the present study, a randomized controlled trial (RCT) is used to assess the effectiveness of MCT in comparison to ERP in an outpatient clinical sample of patients with OCD. Results: Both MCT and ERP produced significant pre-treatment to post-treatment decreases in obsessive-compulsive, comorbid psychological symptoms and metacognitive beliefs, both with moderate to large within-group effect sizes and high proportions of significant clinical change. Drop-out rates were low and treatment gains were maintained at six-month follow-up. There were no differences in efficacy observed between MCT and ERP treatments. Conclusions: MCT proves to be a promising treatment of OCD.</p

The Assessment of Thought Fusion Beliefs and Beliefs About Rituals:Psychometric Properties of the Thought Fusion Instrument and Beliefs About Rituals Inventory

Background: According to the metacognitive model, two domains of metacognitive beliefs play a role in the development and maintenance of obsessive-compulsive disorder (OCD). The Thought Fusion Instrument (TFI) has been developed to measure metacognitive beliefs about the significance of intrusive thoughts. The Beliefs About Rituals Inventory (BARI) assesses metacognitive beliefs about the necessity of performing ritual behaviors. Studies assessing the psychometric properties of the TFI and BARI are scarce. There are no studies assessing the factor structure of the TFI and the BARI. Methods: In this study, we assessed the psychometric properties of the TFI and the BARI in nonclinical (n = 141) and clinical populations (OCD [n = 60], anxiety disorder [n = 30], and autism spectrum disorder [n = 50]). In the nonclinical population, the factor structure is also explored. Results: For both the TFI and the BARI, an explorative factor analysis revealed a one-factor solution, which now needs further exploration using confirmative approaches. The internal consistency appeared good, and they had a moderate test–retest reliability. Convergent and divergent validity of the instruments appeared sufficient, but more research is required to draw firm conclusions. The criterion validity turned out to be moderate for the BARI but low for the TFI in measuring OCD-specific metacognitions. Conclusions: Based on the explorative factor analysis, we hypothesize the TFI and the BARI to measure a single-factor construct. The current study shows that the TFI and the BARI are potentially suitable questionnaires to assess metacognitions in clinical and nonclinical populations. More research is required before clear recommendations can be made for the utility and use in clinical practice.</p

Metacognitieve therapie voor de obsessieve-compulsieve stoornis

De obsessieve-compulsieve stoornis (OCS) is een veelvoorkomende en invaliderende stoornis. Cognitieve gedragstherapie (CGT) in de vorm van exposure met responspreventie (ERP) is de psychologische behandeling van eerste voorkeur. Ondanks de aangetoonde werkzaamheid van ERP is verbetering van de effectivitei

The effectiveness of metacognitive therapy in comparison to exposure and response prevention for obsessive-compulsive disorder:A randomized controlled trial

Background: The recommended psychological treatment of choice for obsessive-compulsive disorder (OCD) is exposure with response prevention (ERP). Although this treatment is quite effective, recovery rates are modest and attrition rate is relatively high. Also, ERP treatment requires amounts of therapist time. A possible way to improve OCD treatment is by taking into account key cognitive processes involved in the development and maintenance of the disorder. The metacognitive model is such an account and pilot findings suggest that the associated metacognitive therapy (MCT) might be an effective treatment for OCD. Methods: In the present study, a randomized controlled trial (RCT) is used to assess the effectiveness of MCT in comparison to ERP in an outpatient clinical sample of patients with OCD. Results: Both MCT and ERP produced significant pre-treatment to post-treatment decreases in obsessive-compulsive, comorbid psychological symptoms and metacognitive beliefs, both with moderate to large within-group effect sizes and high proportions of significant clinical change. Drop-out rates were low and treatment gains were maintained at six-month follow-up. There were no differences in efficacy observed between MCT and ERP treatments. Conclusions: MCT proves to be a promising treatment of OCD.</p

Temporal and spatial changes in wall shear stress during atherosclerotic plaque progression in mice

Wall shear stress (WSS) is involved in atherosclerotic plaque initiation, yet its role in plaque progression remains unclear. We aimed to study (i) the temporal and spatial changes in WSS over a growing plaque and (ii) the correlation between WSS and plaque composition, using animal-specific data in an atherosclerotic mouse model. Tapered casts were placed around the right common carotid arteries (RCCA) of ApoE−/− mice. At 5, 7 and 9 weeks after cast placement, RCCA geometry was reconstructed using contrast-enhanced micro-CT. Lumen narrowing was observed in all mice, indicating the progression of a lumen intruding plaque. Next, we determined the flow rate in the RCCA of each mouse using Doppler Ultrasound and computed WSS at all time points. Over time, as the plaque developed and further intruded into the lumen, absolute WSS significantly decreased. Finally at week 9, plaque composition was histologically characterized. The proximal part of the plaque was small and eccentric, exposed to relatively lower WSS. Close to the cast a larger and concentric plaque was present, exposed to relatively higher WSS. Lower WSS was significantly correlated to the accumulation of macrophages in the eccentric plaque. When pooling data of all animals, correlation between WSS and plaque composition was weak and no longer statistically significant. In conclusion, our data showed that in our mouse model absolute WSS strikingly decreased during disease progression, which was significantly correlated to plaque area and macrophage content. Besides, our study demonstrates the necessity to analyse individual animals and plaques when studying correlations between WSS and plaque composition

Contrast-enhanced micro-CT imaging in murine carotid arteries: A new protocol for computing wall shear stress

Background: Wall shear stress (WSS) is involved in the pathophysiology of atherosclerosis. The correlation between WSS and atherosclerosis can be investigated over time using a WSS-manipulated atheroscleroti

The interplay of collagen, macrophages, and microcalcification in atherosclerotic plaque cap rupture mechanics

The rupture of an atherosclerotic plaque cap overlying a lipid pool and/or necrotic core can lead to thrombotic cardiovascular events. In essence, the rupture of the plaque cap is a mechanical event, which occurs when the local stress exceeds the local tissue strength. However, due to inter- and intra-cap heterogeneity, the resulting ultimate cap strength varies, causing proper assessment of the plaque at risk of rupture to be lacking. Important players involved in tissue strength include the load-bearing collagenous matrix, macrophages, as major promoters of extracellular matrix degradation, and microcalcifications, deposits that can exacerbate local stress, increasing tissue propensity for rupture. This review summarizes the role of these components individually in tissue mechanics, along with the interplay between them. We argue that to be able to improve risk assessment, a better understanding of the effect of these individual components, as well as their reciprocal relationships on cap mechanics, is required. Finally, we discuss potential future steps, including a holistic multidisciplinary approach, multifactorial 3D in vitro model systems, and advancements in imaging techniques. The obtained knowledge will ultimately serve as input to help diagnose, prevent, and treat atherosclerotic cap rupture.</p

Imaging inflammation in atherosclerotic plaques, targeting SST2 with [111In]In-DOTA-JR11

Background: Imaging Somatostatin Subtype Receptor 2 (SST2) expressing macrophages by [DOTA,Tyr3]-octreotate (DOTATATE) has proven successful for plaque detection. DOTA-JR11 is a SST2 targeting ligand with a five times higher tumor uptake than DOTATATE, and holds promise to improve plaque imaging. The aim of this study was to evaluate the potential of DOTA-JR11 for plaque detection. Methods and Results: Atherosclerotic ApoE−/− mice (n = 22) fed an atherogenic diet were imaged by SPECT/CT two hours post injection of [111In]In-DOTA-JR11 (~ 200 pmol, ~ 50 MBq). In vivo plaque uptake of [111In]In-DOTA-JR11 was visible in all mice, with a target-to-background-ratio (TBR) of 2.23 ± 0.35. Post-mortem scans after thymectomy and ex vivo scans of the arteries after excision of the arteries confirmed plaque uptake of the radioligand with TBRs of 2.46 ± 0.52 and 3.43 ± 1.45 respectively. Oil red O lipid-staining and ex vivo autoradiography of excised arteries showed [111In]In-DOTA-JR11 uptake at plaque locations. Histological processing showed CD68 (macrophages) and SST2 expressing cells in plaques. SPECT/CT, in vitro autoradiography and immunohistochemistry performed on slices of a human carotid endarterectomy sample showed [111In]In-DOTA-JR11 uptake at plaque locations containing CD68 and SST2 expressing cells. Conclusions: The results of this study indicate DOTA-JR1