Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011.

Intima-media thickness (IMT) provides a surrogate end point of cardiovascular outcomes in clinical trials evaluating the efficacy of cardiovascular risk factor modification. Carotid artery plaque further adds to the cardiovascular risk assessment. It is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness >1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. The scientific basis for use of IMT in clinical trials and practice includes ultrasound physics, technical and disease-related principles as well as best practice on the performance, interpretation and documentation of study results. Comparison of IMT results obtained from epidemiological and interventional studies around the world relies on harmonization on approaches to carotid image acquisition and analysis. This updated consensus document delineates further criteria to distinguish early atherosclerotic plaque formation from thickening of IMT. Standardized methods will foster homogenous data collection and analysis, improve the power of randomized clinical trials incorporating IMT and plaque measurements and facilitate the merging of large databases for meta-analyses. IMT results are applied to individual patients as an integrated assessment of cardiovascular risk factors. However, this document recommends against serial monitoring in individual patients.

Effect of combined ultrasound and microbubbles treatment in an experimental model of cerebral ischemia.

Combined 2-MHz ultrasound (US) and second-generation, sulfur hexafluoride microbubbles (MB) treatment (US+MB) was performed in a permanent middle cerebral artery (MCA) occlusion model in rats to evaluate possible effects on the ischemic cascade. We used 16 Wistar rats and the MCA occlusion model for stroke induction. Glutamate, pyruvate, lactate and glycerol levels were measured by intracerebral microdialysis before and after stroke induction and after US+MB application (n = 8) for 20 h. After 24 h, brain infarct volume, apoptosis and IL-6 and TNF-alpha levels were evaluated. The infarct volume was significantly reduced (p < 0.05) in the US+MB-treated group compared with control animals. In additional, glutamate levels were significantly lower in US+MB-treated animals, and these animals showed a higher rate of apoptotic cell death in the infarcted area. The levels of IL-6 and TNF-alpha concentrations were not different in both groups, and there was no apoptotic cell death outside the infarction in animals treated with US+MB. The results demonstrate that US+MB with second generation microbubbles does not have a harmful effect on ischemic stroke in an MCA occlusion model of the rat.

[Correlation of duplex sonographic stenosis grading by means of cross-sectional analysis and MR-tomographic blood volume flow quantification in unilateral stenosis of the internal carotid artery]. / Korrelation von duplexsonographischer Stenosegraduierung mittels Querschnittsflächenbestimmung und MR-tomographischer Blutvolumenflussquantifizierung bei unilateraler Stenose der Arteria carotis interna.

PURPOSE: Correlation of duplex ultrasonographic grading of unilateral internal carotid artery (ICA) stenosis and ICA blood volume flow (BVF) quantification. MATERIALS AND METHODS: Using a 2D cine phase-contrast MR technique, 62 patients with unilateral ICA stenosis at the level of the bifurcation between 50 % and 98 % and 20 age-matched normal controls were examined. BVF was measured in the stenosed ICA. Ultrasonographic grading of stenoses was based on cross-sectional duplex sonography (color Doppler flow imaging [CDFI], real-time compound imaging) and compared to the changes in BVF in the stenosed ICA. RESULTS: There was no statistically significant difference in BVF in stenoses of the ICA up to 70 % and in normal controls. ICA stenoses greater 70 % began to be hemodynamically relevant. With increasing stenosis, a decrease in BVF in the ipsilateral ICA was determined with a high and linear correlation of r = - 0.83. Normal controls showed a BVF in an ICA of 247.0 +/- 32.0 ml/min, patients with 70 % stenosis a mean BVF of 225.3 +/- 32.2 ml/min (P = 0.4) without significant reduction, patients with 80 % stenosis a significant reduction of BVF to a mean flow of 184.0 +/- 53.8 ml/min (P < 0.005), patients with 90 % stenosis a reduction of the mean BVF in the stenosed ICA to 84.6 +/- 41.9 ml/min (P < 0.0005) and patients with stenoses > 95 % a mean BVF of only 26.0 +/- 4.0 ml/min (P < 0.0005). In patients with unilateral ICA stenosis greater than 81 %, a significant decrease of BVF in the stenosed ICA was documented. CONCLUSION: Comparison of ultrasonographic grading of unilateral ICA stenosis and BVF determination in patients with ICA stenoses demonstrate a high correlation between increase in the stenosis and decrease in the ipsilateral blood flow beginning at 70 % stenosis. ICA stenoses greater than 80 % are significantly hemodynamically relevant.

Reconstruction and visualization of irregularly sampled three- and four-dimensional ultrasound data for cerebrovascular applications.

Although recent studies have demonstrated the potential value of compounded data for improvement in signal-to-noise ratio and speckle contrast for three-dimensional (3-D) ultrasonography, clinical applications are lacking. We investigated the potential of six degrees-of-freedom (6-DOF) scanhead position and orientation measurement (POM) devices for registration of in vivo multiplanar, irregularly sampled ultrasound (US) images to a regular 3-D volume space. The results demonstrate that accurate spatial and temporal registration of four-dimensional (4-D) US data can be achieved using a 6-DOF scanhead tracking system. For reconstruction of arbitrary, irregularly sampled US data, we introduce a technique based upon a weighted, ellipsoid Gaussian convolution kernel. Volume renderings of 3-D and 4-D compounded in vivo US data are presented. The results, although restricted to the field of cerebrovascular disease, will be of value to other applications of 3-D sonography, particularly those in which compounding of data through irregular sampling may provide superior information on tissue or vessel structure.

Beta-2-microglobulin adsorption and release in-vitro: influence of membrane material, osmolality and heparin.

We studied the effects of cuprammonium rayon (CR), polyacrylonitrile (PAN), polysulfone (PS), changes in osmolality, and heparin dosage on beta-2-microglobulin (b2M) handling in an in-vitro model that excluded convective transport and minimized diffusive transport. Both PAN and PS exhibited high adsorption capacity for b2M. Osmolality changes had no effect on b2M adsorption or release. CR membrane adsorption was minimal but increased slightly when higher heparin doses were used. In experiments with CR and high heparin doses (4 U/ml) b2M release occurred during the first 15 minutes of in-vitro dialysis, but this increase was inhibited by removing the leukocytes from the blood, indicating that b2M is released from leukocytes.

Neurons but not glial cells overexpress ubiquitin in the rat brain following focused ultrasound-induced opening of the blood-brain barrier.

Focused ultrasound-induced opening of the blood-brain barrier (BBB) in the presence of ultrasound contrast agents is a promising strategy for a targeted drug delivery to the brain. The aim of our study was to identify whether brain molecular stress pathways are targeted by ultrasound treatment. Using an upper level of acoustic pressures in combination with microbubbles, which have been previously reported as reliable for BBB opening without causing tissue damage, we found that ultrasound leads to an increased ubiquitinylation of proteins in neuronal (11+/-3 ubiquitin-overexpressing cells per optical field) but not glial cells 6 h post-insonation, increasing to 16 (+/-4) labelled cells after 24 h. No changes in the expression of Hsp70 and Hsc70 were detected over 24 h. Ultrasound treatment was followed by limited apoptosis after 24 h (32+/-6 cleaved-caspase 3-positive cells per optical field) in the insonated areas. Only neurons were identified in the apoptotic population. Although these observations may not be applicable for all acoustic parameters useful for BBB opening, they demonstrate that insonation of the rat brain with the parameters used in our experiments is a useful tool for BBB opening and induces specific cellular stress response restricted to neuronal cells.

Mannheim carotid intima-media thickness consensus (2004-2006). An update on behalf of the Advisory Board of the 3rd and 4th Watching the Risk Symposium, 13th and 15th European Stroke Conferences, Mannheim, Germany, 2004, and Brussels, Belgium, 2006.

Intima-media thickness (IMT) is increasingly used as a surrogate end point of vascular outcomes in clinical trials aimed at determining the success of interventions that lower risk factors for atherosclerosis and associated diseases (stroke, myocardial infarction and peripheral artery diseases). The necessity to promote further criteria to distinguish early atherosclerotic plaque formation from thickening of IMT and to standardize IMT measurements is expressed through this updated consensus. Plaque is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness >1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. Standard use of IMT measurements is based on physics, technical and disease-related principles as well as agreements on how to perform, interpret and document study results. Harmonization of carotid image acquisition and analysis is needed for the comparison of the IMT results obtained from epidemiological and interventional studies around the world. The consensus concludes that there is no need to 'treat IMT values' nor to monitor IMT values in individual patients apart from exceptions named, which emphasize that inside randomized clinical trials should be performed. Although IMT has been suggested to represent an important risk marker, according to the current evidence it does not fulfill the characteristics of an accepted risk factor. Standardized methods recommended in this consensus statement will foster homogenous data collection and analysis. This will help to improve the power of randomized clinical trials incorporating IMT measurements and to facilitate the merging of large databases for meta-analyses.

[Retrospective analysis of neurological patients on a medical intensive care unit]. / Retrospektive Analyse der Versorgung neurologischer Patienten einer internistischen Intensivstation.

OBJECTIVE: The aim of this study was to evaluate number and kind of neurological patients in comparison with other patients on a medical ICU. METHODS: Over a period of one year, all neurological intensive care patients on a medical ICU were evaluated according to age, sex, diagnosis, mortality, diagnostic methods, ventilation and referral to other hospitals and general wards. RESULTS: Comparable to a specialist neurological ICU a wide spectrum of neurological diseases could be observed on an interdisciplinary ICU. In comparison to other patient groups, patients with neurological disease had a higher rate of ventilation, a longer hospital stay and a higher mortality. CONCLUSION: Our data also demonstrate the relevant amount of neurological patients (19 % measured by bed assignment) in comparison to all patients, and the specific neurological procedures were applicable on a medical/interdisciplinary ICU. A higher interest for neurological patient on a medical ICU would therefore be essential.

Power Doppler evaluation of revascularization in childhood moyamoya.

Moyamoya disease is generally recognized in young children. One potential treatment is direct extra-intracranial bypass combined with indirect revascularization using encephalo-myo-synangiosis. Standard follow-up to assess neoangiogenesis includes repeat cerebral angiography, which is invasive. The authors studied whether noninvasive power Doppler imaging could evaluate the patency of the bypass and the degree of indirect revascularization. They found that transcranial power Doppler imaging is a valid noninvasive alternative to cerebral angiography.

Imaging arterial wall disease.

Ultrasonographic imaging of the carotid arteries allows assessment of both early and advanced atherosclerotic disease. This noninvasive technique has played a central role in many recent epidemiological studies and is being used increasingly for evaluating the efficacy of atherosclerosis prevention trials. New developments in ultrasound equipment, the use of echocontrast agents, novel applications of three- and four-dimensional sonography and in vivo characterization of plaque constituents with high-resolution MRI have broadened the scope of imaging of arterial walls, providing both enhanced information on disease progression as well as new insights into pathomechanisms of carotid plaque embolization. This article highlights pertinent issues of imaging of arterial wall disease and discusses important areas of current and future research in this field.

Four-dimensional ultrasonographic characterization of plaque surface motion in patients with symptomatic and asymptomatic carotid artery stenosis.

BACKGROUND AND PURPOSE: In vitro studies of atherosclerotic plaque fracture mechanics suggest that analysis of local variations in surface deformability may provide information on relative vulnerability to plaque fissuring or rupture. We investigated plaque surface deformations in patients with symptomatic and asymptomatic carotid artery disease using 4-dimensional ultrasonography and techniques for measuring optical flow. METHODS: Four-dimensional ultrasound examinations of carotid artery plaques were performed in 23 asymptomatic and 22 symptomatic patients with 50% to 90% stenosis of the internal carotid artery. Plaque surface motion during 1 cardiac cycle was computed with a hierarchical model-based motion estimator. Results were compared with plaque echogenicity and surface structure. RESULTS: Of the 45 patients examined, plaque surface motion estimates were obtained for 18 asymptomatic and 13 symptomatic patients. There were no significant differences in echogenicity or surface structure of asymptomatic and symptomatic plaques (P>0.05). Results of motion estimation showed that asymptomatic plaques had surface motion vectors of equal orientation and magnitude to those of the internal carotid artery, whereas symptomatic plaques demonstrated evidence of inherent plaque movement. There was no significant difference in maximal plaque velocity between symptomatic and asymptomatic plaques (P<0.14). Maximal discrepant surface velocity (MDSV) in symptomatic plaques was 3.85+/-1.26 mm/s (mean+/-SD), which was significantly higher (P<0.001) than MDSV of asymptomatic plaques with 0.58+/-0.42 mm/s (mean+/-SD). CONCLUSIONS: ++MDSV of carotid artery plaques is significantly different in asymptomatic and symptomatic disease. Further studies are warranted to determine whether plaque surface motion patterns can identify vulnerable plaques in patients with carotid artery stenosis.

[Aspirin dosage for prevention of cerebral infarct: arguments for low dosage]. / ASS-Dosierung zur Prävention zerebraler Insulte: Argumente für eine niedrige Dosierung.

Acetylsalicylic acid (ASS) is one of the best examined substances used in secondary prevention after TIA and stroke. Since different strategies and measurement variables were used in numerous randomised, double-blind, placebo-controlled studies (one end-variable, such as non-fatal stroke, myocardium infarction and vascular mortality, or combined end-variables, such as TIA, stroke and death), meta-analysis was necessary to prove that ASS resulted in about 22% reduction of secondary stroke. There is disagreement over the optimal dosage to prevent a stroke: earlier studies considered > or = 975 mg ASS per day, sometimes in combination with other substances, while more recently, lower dosages of about 300 mg per day or even as low as < or = 100 mg per day have been proposed. Higher and lower dosages were effective compared with placebo but with no significant difference in risk reduction, despite the trend towards a transient but insignificant reduction of secondary events for the high dosage. All available studies demonstrated a strictly dose-related gastro-intestinal hemorrhagic bleeding complication rate. Since no data are available from a direct comparison in a large sample size trial to prove the superiority of low-dose ASS (< or = 300 mg per day) over high dosages (> or = 975 mg per day) in secondary prevention of stroke, we believe that the lowest dosage of < or = 100 mg per day should be recommended for safety reasons.

Pathophysiologic assessment of data from a stroke data bank.

Stroke data banks have been instrumental in helping us to clarify stroke etiology and in the investigation of clinical-topographic correlations. For these purposes they have relied upon results from noninvasive vascular and cardiac methods, including extra- and transcranial Doppler sonography and echocardiography, as well as from procedures such as cranial computed tomography and magnetic resonance imaging. Conventional database concepts have also been used to assess pathophysiologic aspects of stroke. Although such applications have made important contributions in this multidiscipline area of investigation, they are limited by a lack of explicit representation of pathophysiologic knowledge for data interpretation. Recent results from artificial intelligence research suggest exciting new frontiers for medical database design with concepts stemming from second generation expert systems. We propose an extended concept for stroke data banks to include a knowledge-based system which incorporates current patient data, heuristic knowledge relating clinical features to functional impairment, and pathophysiologic models of neurological disease.

Cerebrovascular ultrasound.

Rapid progress in noninvasive ultrasound techniques has resulted in a wide variety of clinical applications for assessment of both extracranial and intracranial arterial diseases. Recent highlights in cerebrovascular ultrasound research include imaging methods for characterization of intracranial aneurysms, use of echocontrast agents for improved evaluation of acute stroke patients and transient response harmonic imaging for depiction of brain perfusion. The important role of transcranial Doppler microembolism detection in carotid endarterectomy has been defined, new approaches to noninvasive Doppler measurement of intracranial pressure are progressing, and the clinical indications for transcranial Doppler monitoring of intracranial vasospasm to prevent secondary stroke have expanded. New functional transcranial Doppler applications, which are complementary to positron emission tomography and functional magnetic resonance imaging studies, are evolving for evaluation of functional recovery after stroke; investigation of perfusion asymmetries during complex spatial tasks; assessment of hemispheric dominance in surgical candidates for epilepsy surgery; and elucidation of temporal patterns of regional neuronal activity. With increasing sophistication of cerebrovascular ultrasound methodology, it is essential that standards for data acquisition and interpretation be established. Three recent consensus meetings have provided detailed recommendations on quantification of carotid artery stenosis, on characterization of carotid artery plaques and on microembolism detection by transcranial Doppler.

New and future developments in cerebrovascular ultrasound, magnetic resonance angiography, and related techniques.

Four-dimensional (4D) analysis of atherosclerotic plaque and wall motion, the application of 4D ultrasound to the study of atherogenesis, and the incorporation of ultrasound data into flow models for simulation of cerebrovascular hemodynamics are new frontiers in diagnostic ultrasound that use computer vision and optical flow techniques to exploit the full potential of real-time imaging and Doppler studies. New approaches to improve blood vessel delineation with ultrasound include application of contrast agents, harmonic imaging, and red blood cell density imaging. An assessment of the potential clinical utility of these new developments in cerebrovascular ultrasound requires an analysis of comparable trends in magnetic resonance (MR) technology, eg, rapid advances in the fields of MR angiography, dynamic contrast-enhanced MR, and MR diffusion imaging. Likewise, the value of ultrasound techniques for the measurement of blood flow to evaluate cerebrovascular hemodynamics must be compared to related methods in magnetic resonance, such as dynamic MR inflow tracking. This article addresses several new and future developments in cerebrovascular ultrasound and discusses their relative merits in terms of ongoing research in the field of magnetic resonance angiography, imaging, and related techniques.

Sonographic assessment of carotid artery stenosis. Comparison of power Doppler imaging and color Doppler flow imaging.

BACKGROUND AND PURPOSE: Power Doppler imaging (PDI) is a new ultrasound technique that, in contrast to color Doppler flow imaging (CDFI), generates intravascular color signals from the reflected echo amplitude depending mainly on the density of red blood cells. We evaluated the diagnostic significance of PDI compared with CDFI for the measurement of carotid stenosis and characterization of plaque surface. METHODS: In 25 internal carotid artery stenoses, reduction of the intrastenotic lumen contrasted by blood density signals and color Doppler signals on longitudinal and transverse views was assessed for correlative evaluation. In addition, the peak systolic flow velocity of the Doppler spectrum was correlated with PDI and CDFI measurements. RESULTS: PDI provided good visualization of the residual lumen in all stenoses, whereas displays on CDFI were inadequate in two calcified plaques. PDI revealed two ulcerative stenoses classified as smooth on CDFI. The correlation between PDI and CDFI was high for measurement of area stenosis (r = .93) and moderate for diameter stenosis (r = .73). Similarly, cross-sectional reduction on both imaging methods correlated more significantly with peak systolic flow velocity than diameter reduction. CONCLUSIONS: This pilot study suggests that PDI provides additional information for luminal measurement and characterization of plaque surface in complicated high-grade carotid stenosis. Because of the absent visualization of hemodynamics, PDI should be used in combination with CDFI.

MRI of transient osteoporosis of the hip.

Among the available imaging techniques such as conventional radiography, radionuclide bone scan, and computed tomography (CT), magnetic resonance imaging (MRI) has made significant contributions to the diagnosis of acute hip joint disease in adults by enabling early differentiation between such conditions as idiopathic avascular femoral head necrosis, septic coxitis, degenerative disease, and tumors. In this study we investigated the use of MRI for evaluation of patients with transient osteoporosis (TO). MRI with T1- and T2-weighted sequences in coronal, transverse, and sagittal sections was performed in 12 patients with retrospectively confirmed TO, both at the onset of the disease and later as follow-up procedure. MRI revealed three typical stages of TO: a diffuse stage, a focal stage, and a residual stage. Characteristic symptoms of TO are hip pain and a need for protective splinting of the hip joint. Conventional radiographs show demineralization of the hip joint without joint space narrowing. Clinical, radiologic, and MRI findings normalize within 6-10 months, indicating that TO has a good prognosis with complete restoration of bone density.