Integration of visual and non-visual self-motion cues during voluntary head movements in the human brain.

Our phenomenological experience of the stable world is maintained by continuous integration of visual self-motion with extra-retinal signals. However, due to conventional constraints of fMRI acquisition in humans, neural responses to visuo-vestibular integration have only been studied using artificial stimuli, in the absence of voluntary head-motion. We here circumvented these limitations and let participants to move their heads during scanning. The slow dynamics of the BOLD signal allowed us to acquire neural signal related to head motion after the observer's head was stabilized by inflatable aircushions. Visual stimuli were presented on head-fixed display goggles and updated in real time as a function of head-motion that was tracked using an external camera. Two conditions simulated forward translation of the participant. During physical head rotation, the congruent condition simulated a stable world, whereas the incongruent condition added arbitrary lateral motion. Importantly, both conditions were precisely matched in visual properties and head-rotation. By comparing congruent with incongruent conditions we found evidence consistent with the multi-modal integration of visual cues with head motion into a coherent "stable world" percept in the parietal operculum and in an anterior part of parieto-insular cortex (aPIC). In the visual motion network, human regions MST, a dorsal part of VIP, the cingulate sulcus visual area (CSv) and a region in precuneus (Pc) showed differential responses to the same contrast. The results demonstrate for the first time neural multimodal interactions between precisely matched congruent versus incongruent visual and non-visual cues during physical head-movement in the human brain. The methodological approach opens the path to a new class of fMRI studies with unprecedented temporal and spatial control over visuo-vestibular stimulation.

Real-motion signals in human early visual cortex.

Eye movements induce visual motion that can complicate the stable perception of the world. The visual system compensates for such self-induced visual motion by integrating visual input with efference copies of eye movement commands. This mechanism is central as it does not only support perceptual stability but also mediates reliable perception of world-centered objective motion. In humans, it remains elusive whether visual motion responses in early retinotopic cortex are driven by objective motion or by retinal motion associated with it. To address this question, we used fMRI to examine functional responses of sixteen visual areas to combinations of planar objective motion and pursuit eye movements. Observers were exposed to objective motion that was faster, matched or slower relative to pursuit, allowing us to compare conditions that differed in objective motion velocity while retinal motion and eye movement signals were matched. Our results show that not only higher level motion regions such as V3A and V6, but also early visual areas signaled the velocity of objective motion, hence the product of integrating retinal with non-retinal signals. These results shed new light on mechanisms that mediate perceptual stability and real-motion perception, and show that extra-retinal signals related to pursuit eye movements influence processing in human early visual cortex.

Connectivity Reveals Sources of Predictive Coding Signals in Early Visual Cortex During Processing of Visual Optic Flow.

Superimposed on the visual feed-forward pathway, feedback connections convey higher level information to cortical areas lower in the hierarchy. A prominent framework for these connections is the theory of predictive coding where high-level areas send stimulus interpretations to lower level areas that compare them with sensory input. Along these lines, a growing body of neuroimaging studies shows that predictable stimuli lead to reduced blood oxygen level-dependent (BOLD) responses compared with matched nonpredictable counterparts, especially in early visual cortex (EVC) including areas V1-V3. The sources of these modulatory feedback signals are largely unknown. Here, we re-examined the robust finding of relative BOLD suppression in EVC evident during processing of coherent compared with random motion. Using functional connectivity analysis, we show an optic flow-dependent increase of functional connectivity between BOLD suppressed EVC and a network of visual motion areas including MST, V3A, V6, the cingulate sulcus visual area (CSv), and precuneus (Pc). Connectivity decreased between EVC and 2 areas known to encode heading direction: entorhinal cortex (EC) and retrosplenial cortex (RSC). Our results provide first evidence that BOLD suppression in EVC for predictable stimuli is indeed mediated by specific high-level areas, in accord with the theory of predictive coding.

Intracranial arterial calcifications as a prognostic factor for subsequent major adverse cardiovascular events (MACE).

BACKGROUND: Intracranial arterial calcifications (ICAC) are often detected on unenhanced CT of patients with an age > 60. However, association with the subsequent occurrence of major adverse cardiovascular events (MACE) has not yet been evaluated. PURPOSE: This study aimed at evaluating the association of ICAC with subsequent MACE and overall mortality. METHODS: In this retrospective, IRB approved study, we included 175 consecutive patients (89 males, mean age 78.3 ± 8.5 years) of age > 60 years who underwent an unenhanced CT of the head due to minor trauma or neurological disorders. Presence of ICAC was determined in seven intracranial arteries using a semi-quantitative scale, which resulted in the calcified plaque score (CPS). Clinical follow-up information was obtained by questionnaires and telephone interviews. MACE was defined as myocardial infarction or revascularization, stroke or death due to cardiovascular event. RESULTS: Mean follow-up time was 39.8 ± 7.8 months, resulting in 579.7 patient-years of follow-up. Overall, 36 MACE occurred during follow-up (annual event rate = 6.2%/year). Mean CPS was significantly higher in subjects with MACE during follow-up compared to subjects without MACE (p < 0.01). In 15 patients CPS was 0; in none of these patients MACE was registered. Kaplan-Meier-analysis revealed that patients with a low plaque burden (CPS < 5) had a significant longer MACE-free and overall survival than patients with a high plaque burden (CPS ≥ 5) (p < 0.01). CONCLUSION: Patients with ICAC have an increased risk for future cardio- or cerebrovascular events. Therefore, ICAC might be a prognostic factor to determine the risk for these events in older patients.

Prevalence and distribution of calcified nodules in carotid arteries in correlation with clinical symptoms.

PURPOSE: Calcified nodules ("CN") are responsible for up to 5% of coronary-infarcts and, therefore, classified as minor criteria of "vulnerable" atherosclerotic plaque. We sought to evaluate prevalence and distribution of CN in carotid arteries in correlation with clinical symptoms. METHODS: 178 consecutive patients with unilateral ischemic stroke and carotid plaques ≥2 mm by duplex ultrasound underwent a carotid-black-blood-3T-MRI with fat-saturated pre- and post-contrast T1w-, PDw-, T2w- and TOF images using dedicated surface-coils. CN were defined as distinct calcification with an irregular, protruding, and convex luminal surface. Prevalence of CN was determined in common carotid artery ("CCA") and internal carotid artery ("ICA") in consensus by two reviewers blinded to clinical information. RESULTS: Thirty seven CN in 28 arteries of 26 patients were identified. Prevalence of CN in CCA compared to ICA was slightly higher (59 vs. 41%), but nearly similar in 66 arteries with ≥30% compared to 290 arteries with <30% stenosis (9.1 vs. 7.6%) and in the artery ipsilateral versus contralateral to stroke (7.9 vs. 7.9%; P values n.s.). Prevalence of CN was significantly higher in 40 symptomatic arteries with ≥30% stenosis compared to asymptomatic 26 arteries (15.6 vs. 0%; P = 0.04). There was a significantly higher prevalence of hypercholesterolemia and hypertension in patients with CN (57.7 vs. 36.0 and 88.5 vs. 66.7%; P values <0.05). CONCLUSION: CN were found in 7.9% of arteries with carotid-plaques ≥2 mm by duplex-ultrasound; prevalence was significantly higher in symptomatic arteries with ≥30% stenosis compared to asymptomatic with <30% stenosis, suggesting that CN play a role in pathogenesis of ischemic stroke in a small subset of patients.

Visual high-level regions respond to high-level stimulus content in the absence of low-level confounds.

High-level regions of the ventral stream exhibit strong category selectivity to stimuli such as faces, houses, or objects. However, recent studies suggest that at least part of this selectivity stems from low-level differences inherent to images of the different categories. For example, visual outdoor and indoor scenes as well as houses differ in spatial frequency, rectilinearity and obliqueness when compared to face or object images. Correspondingly, scene responsive para-hippocampal place area (PPA) showed strong preference to low-level properties of visual scenes also in the absence of high-level scene content. This raises the question whether all high-level responses in PPA, the fusiform face area (FFA), or the object-responsive lateral occipital compex (LOC) may actually be explained by systematic differences in low-level features. In the present study we contrasted two classes of simple stimuli consisting of ten rectangles each. While both were matched in visual low-level features only one class of rectangle arrangements gave rise to a percept compatible with a high-level 3D layout such as a scene or an object. We found that areas PPA, transverse occipital sulcus (TOS, also referred to as occipital place area, OPA), as well as FFA and LOC showed robust responses to the visual scene class compared to the low-level matched control. Our results suggest that visual category responsive regions are not purely driven by low-level visual features but also by the high-level perceptual stimulus interpretation.

Motion parallax links visual motion areas and scene regions.

When we move, the retinal velocities of objects in our surrounding differ according to their relative distances and give rise to a powerful three-dimensional visual cue referred to as motion parallax. Motion parallax allows us to infer our surrounding's 3D structure as well as self-motion based on 2D retinal information. However, the neural substrates mediating the link between visual motion and scene processing are largely unexplored. We used fMRI in human observers to study motion parallax by means of an ecologically relevant yet highly controlled stimulus that mimicked the observer's lateral motion past a depth-layered scene. We found parallax selective responses in parietal regions IPS3 and IPS4, and in a region lateral to scene selective occipital place area (OPA). The traditionally defined scene responsive regions OPA, the para-hippocampal place area (PPA) and the retrosplenial cortex (RSC) did not respond to parallax. During parallax processing, the occipital parallax selective region entertained highly specific functional connectivity with IPS3 and with scene selective PPA. These results establish a network linking dorsal motion and ventral scene processing regions specifically during parallax processing, which may underlie the brain's ability to derive 3D scene information from motion parallax.

High-risk plaque features can be detected in non-stenotic carotid plaques of patients with ischaemic stroke classified as cryptogenic using combined (18)F-FDG PET/MR imaging.

PURPOSE: The aim of this study was to investigate in 18 patients with ischaemic stroke classified as cryptogenic and presenting non-stenotic carotid atherosclerotic plaques the morphological and biological aspects of these plaques with magnetic resonance imaging (MRI) and (18)F-fluoro-deoxyglucose positron emission tomography ((18)F-FDG PET) imaging. METHODS: Carotid arteries were imaged 150 min after injection of (18)F-FDG with a combined PET/MRI system. American Heart Association (AHA) lesion type and plaque composition were determined on consecutive MRI axial sections (n = 460) in both carotid arteries. (18)F-FDG uptake in carotid arteries was quantified using tissue to background ratio (TBR) on corresponding PET sections. RESULTS: The prevalence of complicated atherosclerotic plaques (AHA lesion type VI) detected with high-resolution MRI was significantly higher in the carotid artery ipsilateral to the ischaemic stroke as compared to the contralateral side (39 vs 0 %; p = 0.001). For all other AHA lesion types, no significant differences were found between ipsilateral and contralateral sides. In addition, atherosclerotic plaques classified as high-risk lesions with MRI (AHA lesion type VI) were associated with higher (18)F-FDG uptake in comparison with other AHA lesions (TBR = 3.43 ± 1.13 vs 2.41 ± 0.84, respectively; p < 0.001). Furthermore, patients presenting at least one complicated lesion (AHA lesion type VI) with MRI showed significantly higher (18)F-FDG uptake in both carotid arteries (ipsilateral and contralateral to the stroke) in comparison with carotid arteries of patients showing no complicated lesion with MRI (mean TBR = 3.18 ± 1.26 and 2.80 ± 0.94 vs 2.19 ± 0.57, respectively; p < 0.05) in favour of a diffuse inflammatory process along both carotid arteries associated with complicated plaques. CONCLUSION: Morphological and biological features of high-risk plaques can be detected with (18)F-FDG PET/MRI in non-stenotic atherosclerotic plaques ipsilateral to the stroke, suggesting a causal role for these plaques in stroke. Combined (18)F-FDG PET/MRI systems might help in the evaluation of patients with ischaemic stroke classified as cryptogenic.

Expansive arterial remodeling of the carotid arteries and its effect on atherosclerotic plaque composition and vulnerability: an in-vivo black-blood 3T CMR study in symptomatic stroke patients.

BACKGROUND: Based on intravascular ultrasound of the coronary arteries expansive arterial remodeling is supposed to be a feature of the vulnerable atheroslerotic plaque. However, till now little is known regarding the clinical impact of expansive remodeling of carotid lesions. Therefore, we sought to evaluate the correlation of expansive arterial remodeling of the carotid arteries with atherosclerotic plaque composition and vulnerability using in-vivo Cardiovascular Magnetic Resonance (CMR). METHODS: One hundred eleven symptomatic patients (74 male/71.8 ± 10.3y) with acute unilateral ischemic stroke and carotid plaques of at least 2 mm thickness were included. All patients received a dedicated multi-sequence black-blood carotid CMR (3Tesla) of the proximal internal carotid arteries (ICA). Measurements of lumen, wall, outer wall, hemorrhage, calcification and necrotic core were determined. Each vessel-segment was classified according to American Heart Association (AHA) criteria for vulnerable plaque. A modified remodeling index (mRI) was established by dividing the average outer vessel area of the ICA segments by the lumen area measured on TOF images in a not affected reference segment at the distal ipsilateral ICA. Correlations of mRI and clinical symptoms as well as plaque morphology/vessel dimensions were evaluated. RESULTS: Seventy-eight percent (157/202) of all internal carotid arteries showed atherosclerotic disease with AHA Lesion-Type (LT) III or higher. The mRI of the ICA was significantly different in normal artery segments (AHA LT I; mRI 1.9) compared to atherosclerotic segments (AHA LT III-VII; mRI 2.5; p < 0.0001). Between AHA LT III-VII there was no significant difference of mRI. Significant correlations (p < 0.05) of the mRI with lumen-area (LA), wall-area (WA), vessel-area (VA) and wall-thickness (WT), necrotic-core area (NC), and ulcer-area were observed. With respect to clinical presentation (symptomatic/asymptomatic side) and luminal narrowing (stenotic/non-stenotic) no relevant correlations or significant differences regarding the mRI were found. CONCLUSION: Expansive arterial remodeling exists in the ICA. However, no significant association between expansive arterial remodeling, stroke symptoms, complicated AHA VI plaque, and luminal stenosis could be established. Hence, results of our study suggest that expansive arterial remodeling is not a very practical marker for plaque vulnerability in the carotid arteries.

Reproducibility and differentiation of cervical arteriopathies using in vivo high-resolution black-blood MRI at 3 T.

INTRODUCTION: The aims of the present study are to evaluate the potential of high-resolution black-blood MRI (hr-bb-cMRI) to differentiate common cervical arteriopathies and to evaluate interobserver reproducibility. METHODS: Forty-three consecutive patients with distinct cervical arteriopathies were examined with cervical hr-bb-cMRI at 3.0 Te with fat-saturated pre- and post-contrast T1w, T2w, and TOF images using dedicated carotid surface coils at our institution. Twenty-three patients had atherosclerotic disease, causing significant stenosis in 12 patients while 11 patients had moderate stenosis. Eight patients presented with cervical vasculitis, and five patients had arterial dissection. Furthermore, seven control subjects with no evidence of carotid disease were included. Two experienced readers blinded to all clinical information reviewed all MR images and classified both carotid and vertebral arteries as affected either by atherosclerosis, dissection, vasculitis, or no disease. Finally, a consensus reading was performed. RESULTS: On a per-vessel level, test performance parameters (sensitivity, specificity, positive predictive value, negative predictive value) were 95, 97.7, 92.9, and 98.5 % for atherosclerotic disease; 91, 100, 100, and 98.7 % for vasculitis; and 100, 100, 100, and 100 % for dissection, respectively. On a per-patient level, performance parameters were 95.7, 85.7, 97.2, and 85.7 % for the diagnosis of atherosclerosis and 100, 100, 100, and 100 % for the diagnosis of dissection and of vasculitis, respectively. Accuracy rates were all above 95 % for all entities. There was a high agreement between observers both in a per-vessel (κ = 0.83) and in a per-patient analysis (κ = 0.82). CONCLUSION: This study demonstrates that hr-bb-cMRI is able to non-invasively differentiate between the most common cervical arteriopathies with an excellent interreader reproducibility.

Exploring Attachment Patterns in Patients With Comorbid Borderline Personality and Substance Use Disorders.

Studies exploring attachment patterns in samples of patients with borderline personality disorder (BPD) report a combination of preoccupied and fearful-avoidant patterns. This has been interpreted as reflecting the approach-avoidance dilemma of BPD. Comorbid substance use disorders (SUD) have not been considered in these studies, despite the high proportions of SUD among BPD patients and despite the more avoidant attachment in SUD samples. This cross-sectional, naturalistic study explores attachment patterns in a sample of comorbid (BPD and SUD) patients, comparing them to two samples of patients with either SUD or BPD only. Within-group comparisons replicated findings of both preoccupied and fearful-avoidant attachment in BPD and comorbid groups. But between-group comparisons showed that comorbid patients were significantly less preoccupied (p = 0.018) and more dismissing-avoidant (p = 0.030). Although both groups were similar in several psychiatric measures, attachment patterns of the comorbid group were more similar to substance abusers than to borderline patients.

A Review on Attachment and Adolescent Substance Abuse: Empirical Evidence and Implications for Prevention and Treatment.

BACKGROUND: This paper reviews research on the relation of attachment and substance use disorders (SUD) in adolescence. Based on a theoretical introduction, we review evidence for a possible general link between SUD and insecure attachment, for links between specific forms of SUD and specific patterns of attachment, and for studies on family patterns of attachment in adolescence. METHODS: Using medical and psychological databases, we identified 10 studies on adolescent SUD and another 13 studies on adult SUD. RESULTS: Empirical evidence strongly supports the assumption of insecure attachment in SUD samples. With regard to specific patterns of attachment, results mainly point towards fearful and dismissing-avoidance, whereas single studies report preoccupied and unresolved patterns. Results indicate different patterns of attachment in different groups of substance abusers, that is, fearful-avoidant attachment in heroin addicts and more heterogeneous results in abusers of other substances. Explorative data suggest different types of insecure family attachment patterns, which might imply different functions of substance abuse and lead to different treatment recommendations. Methodological problems such as poor assessment of SUD and the use of different measures of attachment limit comparability. CONCLUSIONS: Although a lot of research is still needed to address the unknowns in the relation between attachment and SUD, there is strong evidence for a general link between SUD and insecure attachment. Data on connections between different patterns of attachment and different pathways towards SUD are less conclusive but mainly point to disorganized and externalizing pathways. Evidence suggests that fostering attachment security might improve the outcome of state-of-the-art approaches in both early interventional treatment and prevention. Implications for individual and family approaches are outlined.

Iterative image reconstruction techniques for CT coronary artery calcium quantification: comparison with traditional filtered back projection in vitro and in vivo.

PURPOSE: To investigate in vitro and in vivo the use of image-based and raw data-based iterative reconstruction algorithms for quantification of coronary artery calcium by using the Agatston score and subsequent cardiac risk stratification. MATERIALS AND METHODS: In vitro data were obtained by using a moving anthropomorphic cardiac phantom containing calcium inserts of different concentrations and sizes. With institutional review board approval and HIPAA compliance, coronary calcium imaging data of 110 consecutive patients (mean age ± standard deviation, 58.2 years ± 9.8; 48 men) were reconstructed with filtered back projection (FBP), iterative reconstruction in image space (IRIS), and sinogram-affirmed iterative reconstruction (SAFIRE). Image noise was measured and the Agatston score was obtained for all reconstructions. Assignment to Agatston scores and percentile-based cardiac risk categories was compared. Statistical analysis included the Cohen κ coefficient and Friedman and Wilcoxon testing. RESULTS: In vitro, mean Agatston scores ± standard deviation for FBP (638.9 ± 9.6), IRIS (622.7 ± 15.2), and SAFIRE (631.4 ± 17.6) were comparable (P = .30). The smallest phantom calcifications were more frequently detected when iterative reconstruction techniques were used. The Agatston scores in the patient cohort were not significantly different among FBP, IRIS, and SAFIRE in paired comparisons (median Agatston score [25th and 75th percentiles]: 76.0 [20.6, 243.9], 76.4 [22, 249.3], and 75.7 [21.5, 49.1], respectively; P = .20 each). Comparison of categorization based on Agatston score percentiles showed excellent agreement for both IRIS and SAFIRE with FBP (κ = 0.975 [0.942-1.00] and κ = 0.963 [0.922-1.00], respectively). The mean effective dose was 1.02 mSv ± 0.51. Mean image noise was significantly (P < .001) higher with FBP than that with iterative reconstructions. CONCLUSION: In comparison with FBP, iterative reconstruction techniques do not have a profound effect on the reproducible quantification of coronary calcium according to Agatston score and subsequent cardiac risk classification, although risk reclassification may occur in a small subset of subjects.

Computed tomography angiography vs 3 T black-blood cardiovascular magnetic resonance for identification of symptomatic carotid plaques.

BACKGROUND: The purpose of this prospective study was to perform a head-to-head comparison of the two methods most frequently used for evaluation of carotid plaque characteristics: Multi-detector Computed Tomography Angiography (MDCTA) and black-blood 3 T-cardiovascular magnetic resonance (bb-CMR) with respect to their ability to identify symptomatic carotid plaques. METHODS: 22 stroke unit patients with unilateral symptomatic carotid disease and >50% stenosis by duplex ultrasound underwent MDCTA and bb-CMR (TOF, pre- and post-contrast fsT1w-, and fsT2w- sequences) within 15 days of symptom onset. Both symptomatic and contralateral asymptomatic sides were evaluated. By bb-CMR, plaque morphology, composition and prevalence of complicated AHA type VI lesions (AHA-LT6) were evaluated. By MDCTA, plaque type (non-calcified, mixed, calcified), plaque density in HU and presence of ulceration and/or thrombus were evaluated. Sensitivity (SE), specificity (SP), positive and negative predictive value (PPV, NPV) were calculated using a 2-by-2-table. RESULTS: To distinguish between symptomatic and asymptomatic plaques AHA-LT6 was the best CMR variable and presence / absence of plaque ulceration was the best CT variable, resulting in a SE, SP, PPV and NPV of 80%, 80%, 80% and 80% for AHA-LT6 as assessed by bb-CMR and 40%, 95%, 89% and 61% for plaque ulceration as assessed by MDCTA. The combined SE, SP, PPV and NPV of bb-CMR and MDCTA was 85%, 75%, 77% and 83%, respectively. CONCLUSIONS: Bb-CMR is superior to MDCTA at identifying symptomatic carotid plaques, while MDCTA offers high specificity at the cost of low sensitivity. Results were only slightly improved over bb-CMR alone when combining both techniques.

Coding of melodic gestalt in human auditory cortex.

The perception of a melody is invariant to the absolute properties of its constituting notes, but depends on the relation between them-the melody's relative pitch profile. In fact, a melody's "Gestalt" is recognized regardless of the instrument or key used to play it. Pitch processing in general is assumed to occur at the level of the auditory cortex. However, it is unknown whether early auditory regions are able to encode pitch sequences integrated over time (i.e., melodies) and whether the resulting representations are invariant to specific keys. Here, we presented participants different melodies composed of the same 4 harmonic pitches during functional magnetic resonance imaging recordings. Additionally, we played the same melodies transposed in different keys and on different instruments. We found that melodies were invariantly represented by their blood oxygen level-dependent activation patterns in primary and secondary auditory cortices across instruments, and also across keys. Our findings extend common hierarchical models of auditory processing by showing that melodies are encoded independent of absolute pitch and based on their relative pitch profile as early as the primary auditory cortex.

Carotid artery calcium score: Definition, classification, application, and limits.

INTRODUCTION: In the current paper, the "carotid artery calcium score" method is presented with the target to offer a metric method to quantify the amount of calcification in the carotid artery. MODEL AND DEFINITION: The Volume of Interest (VOI) should be extracted and those voxels, with a Hounsfield Unit (HU) value ≥130, should be considered. The total weight value is determined by calculating the sum of the HU attenuation values of all voxels with values ≥130 HU. This value should be multiplied by the conversion factor ("or voxel size") and divided by a weighting factor, the attenuation threshold to consider a voxel as calcified (and therefore 130 HU): this equation determines the Carotid Artery Calcium Score (CACS). RESULTS: In order to provide the demonstration of the potential feasibility of the model, the CACS was calculated in 131 subjects (94 males; mean age 72.7 years) for 235 carotid arteries (in 27 subjects, unilateral plaque was present) considered. The CACS value ranged from 0.67 to 11716. A statistically significant correlation was found (rho value = 0.663, p value = .0001) between the CACS in the right and left carotid plaques. Moreover, a statistically significant correlation between the age and the total CACS was present (rho value = 0.244, p value = .005), whereas no statistically significant difference was found in the distribution of CACS by gender (p = .148). The CACS was also tested at baseline and after contrast and no statistically significant difference was found. CONCLUSION: In conclusion, this method is of easy application, and it weights at the same time the volume and the degree of calcification in a unique parameter. This method needs to be tested to verify its potential utility, similar to the coronary artery calcium score, for the risk stratification of the occurrence of cerebrovascular events of the anterior circulation. Further studies using this new diagnostic tool to determine the prognostic value of carotid calcium quantification are needed.

Dialectical behavior therapy (DBT) in an assertive community treatment structure (ACT): testing integrated care borderline (ICB) in a randomized controlled trial (RECOVER).

BACKGROUND: Though Dialectical Behavior Therapy (DBT) and other treatment models for individuals with Borderline Personality Disorder (BPD) have shown to be efficient in inpatient and outpatient settings, there is a general shortage of these treatments. In Germany, most resources are spent on inpatient treatments and unspecific crisis interventions, while it is difficult to implement the necessary team structures in an outpatient setting. This study is testing an alternative approach focussing on outpatient treatment: Integrated Care Borderline (ICB) provides DBT for persons with severe BPD within the structures of an Assertive Community Treatment (ACT). ICB is team-based, integrating psychiatric and social support as well as crisis interventions into a DBT-strategy. METHODS: ICB was compared to TAU in a prospective, randomized controlled trial. This study is part of RECOVER, a comprehensive stepped care approach in Germany, which enrolled a total of 891 participants. 146 persons were diagnosed with BPD as main diagnosis. Of these, 100 were allocated to the highest level of severe mental illness (SMI) and randomly assigned to either ICB (n = 50) or TAU (n = 50). Data were collected at baseline and 12 months later. The main outcomes were psychosocial functioning (GAF), severity of BPD (BSL-23) and other mental symptoms (BSI, PHQ-9, GAD-7, self-harm), employment status (VILI), as well as hospital days and associated costs. RESULTS: Data show a significant increase of psychosocial functioning and a significant decrease of BPD and other psychiatric symptoms in both groups (r = .28 - .64), without any significant differences between the groups. The proportion of self-harming persons decreased in both groups without statistical significance. Patients were significantly more likely to be employed after a year of treatment in ICB (p = .001), but not in the TAU group (p = .454). Analyses showed a significant difference between the groups (p = .032). Moreover, psychiatric hospital days were significantly reduced in ICB (-89%, p < .001, r = .61), but not in TAU (-41%, p = .276, r = .15), resulting in a significant difference between the groups (p = .016) and in lower annual hospital costs in ICB (5,546€ vs. 10,726€, -48%, p = .011) compared to TAU. CONCLUSION: Our results replicate earlier studies, showing that DBT can be efficient in outpatient settings. Furthermore, they indicate additional effects on employment and hospital days. The ICB-approach seems to offer a viable framework for multiprofessional outpatient DBT-teams. Future research will have to test whether the additional effects are brought about by the additional features of ICB compared to standard outpatient DBT. TRIAL REGISTRATION: Registration number with ClinicalTrials.gov (NCT03459664), RECOVER.

Individualized MRI-based stroke PRediction scOre using plaque Vulnerability for symptomatic carotid artEry disease patients (IMPROVE).

Objective: In TIA and stroke patients with carotid stenosis, estimations of future ipsilateral ischemic stroke risk and treatment decisions are currently primarily based on the degree of stenosis. Intraplaque hemorrhage (IPH), which can be readily visualized on carotid MRI, is increasingly established as an easy to assess and a very strong and independent predictor for ipsilateral stroke risk, stronger than any clinical risk factor. We developed a clinical prediction model (IMPROVE) incorporating IPH, degree of stenosis, and clinical risk factors to select patients with symptomatic carotid stenosis at high risk for stroke. Methods: IMPROVE was developed on pooled clinical and MRI data from five cohort studies of 760 recent TIA or minor stroke patients with carotid plaque who received optimal medical treatment. We used Cox proportional hazards models to determine the coefficients of IMPROVE. IMPROVE was internally validated using bootstrapping and converted to one- and three-year ipsilateral ischemic stroke risk. Results: The development dataset contained 65 ipsilateral incident ischemic strokes that occurred during a median follow-up of 1.2 years (IQR: 0.5-4.1). The IMPROVE model includes five predictors, which are in order of importance: degree of stenosis, presence of IPH on MRI, classification of last event (cerebral vs ocular), sex, and age. Internal validation revealed a good accuracy (C-statistic: 0.82; 95% CI: 0.77-0.87) and no evidence for miscalibration (calibration slope: 0.93). Interpretation: Using presence of IPH on MRI and only four conventional parameters, the IMPROVE model provides accurate individual stroke risk estimates, which may facilitate stratification for revascularization.

Stepped, evidence-based and integrated care service model vs. usual care for mental disorders: A randomized controlled trial (RECOVER).

Stepped, evidence-based and integrated care service models have the potential to be used as a reference for mental health services. RECOVER aimed to evaluate cost savings, effectiveness, and cost-effectiveness of such a model within a two arm, assessor- and data analysist-blinded RCT in Hamburg, Germany. Participants aged 16-79 years with mental disorders were randomly assigned either to RECOVER or treatment as usual (TAU). Primary outcomes comprised costs, effectiveness (combined symptoms, functioning, quality of life), and cost-effectiveness, hierarchically ordered. Outcomes were evaluated according to the ITT principle, group differences regarding costs with adjusted generalized linear models, effectiveness with ANCOVA models, and cost-effectiveness with the incremental cost-effectiveness ratio (ICER) and cost-effectiveness acceptability curves (CEACs). Between 1/1/2018 and 12/31/2020, n = 891 were finally included (n = 477 in RECOVER, n = 444 in TAU). RECOVER was associated with significantly lower annual total costs (-22 %), health and social care costs (-25 %) and hospital costs (-50 %). Effectiveness analyses showed a significantly better outcome for RECOVER with the fully imputed data . The CEACs descriptively demonstrated that RECOVER was cost-effective with a probability of >95 %. Treatment in RECOVER resulted in substantial cost reductions with better cost-effectiveness. RECOVER can be recommended as a reference model for comprehensive and integrated mental health services.

Carotid Plaque-RADS: A Novel Stroke Risk Classification System.

BACKGROUND: Carotid artery atherosclerosis is highly prevalent in the general population and is a well-established risk factor for acute ischemic stroke. Although the morphological characteristics of vulnerable plaques are well recognized, there is a lack of consensus in reporting and interpreting carotid plaque features. OBJECTIVES: The aim of this paper is to establish a consistent and comprehensive approach for imaging and reporting carotid plaque by introducing the Plaque-RADS (Reporting and Data System) score. METHODS: A panel of experts recognized the necessity to develop a classification system for carotid plaque and its defining characteristics. Using a multimodality analysis approach, the Plaque-RADS categories were established through consensus, drawing on existing published reports. RESULTS: The authors present a universal classification that is applicable to both researchers and clinicians. The Plaque-RADS score offers a morphological assessment in addition to the prevailing quantitative parameter of "stenosis." The Plaque-RADS score spans from grade 1 (indicating complete absence of plaque) to grade 4 (representing complicated plaque). Accompanying visual examples are included to facilitate a clear understanding of the Plaque-RADS categories. CONCLUSIONS: Plaque-RADS is a standardized and reliable system of reporting carotid plaque composition and morphology via different imaging modalities, such as ultrasound, computed tomography, and magnetic resonance imaging. This scoring system has the potential to help in the precise identification of patients who may benefit from exclusive medical intervention and those who require alternative treatments, thereby enhancing patient care. A standardized lexicon and structured reporting promise to enhance communication between radiologists, referring clinicians, and scientists.