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Issue 1 (2014) – Supplement 1

Special issue on Neurosonology and Cerebral Hemodynamics

This special issue on Neurosonology and Cerebral Hemodynamics assembles the main breakthroughs presented during the joint 2013 meeting of the European Society of Neurosonology and Cerebral Hemodynamics (ESNCH) and Cerebral Autoregulation Network (CARNet). The various articles published are a reflection of the high scientific standard of the meeting, comprising reviews, viewpoints, original contributions with innovative findings and exciting case reports.

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|    Issue date: 2014-05-09

Guest Editorial

Carving the foremost developments in neurosonology and cerebral hemodynamics from an inspiring meeting - read full article

By: Elsa Azevedo

In May 2013 the international experts on neurosonology and cerebral hemodynamics pooled their knowledge and expertise to produce an historical and fertile scientific meeting. It took the form of a joint meeting between the European Society of Neurosonology and Cerebral Hemodynamics (ESNCH) and the Cerebral Autoregulation Network (CARNet). The meeting hosted over 400 participants from 47 countries of the five continents in over 30 hours of active discussion and major updates in these fields. Following on the success of the reunion, the organizing and scientific committees felt compelled to assemble the major breakthroughs of the event in a publication meant to carve these developments for future reference. The present issue of the International Journal of Clinical Neurosciences and Mental Health began to take shape compiling the various lectures presented throughout the meeting and tutorials, articles with original contributions of innovative findings and exciting case reports.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S01

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Guest Editorial

State-of-the-art and new perspectives in Neurosonology - read full article

By: László Csiba

The neurosonological techniques play an important role in the vascular and non-vascular (degenerative, peripheral nervous system diseases) neurological diseases. The neurosonological methods proved their strength, not only in the prevention and diagnosis of vascular diseases, but also at intensive care unit monitoring and in therapeutic intervention (e.g. sonothrombolysis and gene therapy) in central nervous system diseases. The neurosonological methods detect and follow the early impairment of endothelium function and changes of cerebral hemodynamics before and after pharmacological interventions. This edition summarizes the recent advances of neurosonology, based on the most outstanding presentations of the European Society of Neurosonology and Cerebral Hemodynamics conference organised in Porto, 2013.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S02

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Review Article

Physics of ultrasounds - read full article

By: Victor Oliveira

Neurosonology relies on the use of ultrasounds adapted to the characteristics of the human body, mainly the density of biological structures in order to obtain imaging of vessels, brain parenchyma and muscles as well as the Doppler Effect to study velocities of the blood flow. Aside from the expertise to perform examinations, a sonographer must be aware of the physics behind the machine in order to better understand the capabilities and limitations of these exams. We summarize the most important principles used in neurosonology.

Keywords: Transcranial Doppler, Doppler effect, Blood flow velocity, Fast fourier transform, Pulse repetition frequency.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S03

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Review Article

Ultrasonography of carotid stenosis - read full article

By: Jürgen Klingelhöfer

The classification of internal carotid artery stenosis is of great impact. The degree of stenosis is the main criterion for the decision between an invasive or non- invasive treatment of extracranial internal carotid artery (ICA) stenoses. By now the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria have been internationally approved for radiological grading. According to NASCET the stenosed lumen is compared with the lumen of the distal internal carotid artery. All ultrasound criteria do have limitations and can therefore cause pitfalls in determining the degree of stenosis using one criterion exclusively. Therefore a multi-parametric grading of stenoses should be favored. The multi-parametric “DEGUM” ultrasound criteria have been revised and a novel differentiation between main (primary) and additional (secondary) criteria has been proposed. Recently a similar consensus was reached by the Neurosonology Research Group (NSRG) of the World Federation of Neurology (WFN). Main criteria include the following: imaging of the stenosis in B-mode sonography; visualization of the stenosis by color-coded imaging of flow; measurement of the maximum systolic flow velocity in the area of greatest narrowing of the lumen; systolic flow velocity measurement in the poststenotic segment; assessment of the collateral supply. Additional criteria include the following: indirect findings of an internal carotid artery stenosis in the common carotid artery; evidence of flow disturbances; end-diastolic flow velocity in the area of greatest narrowing of the lumen; the so-called confetti-sign; the carotid ratio. The main advantage of a multi- parametric grading of ICA stenoses is the synergetic effect of the different single criterion. Combining these ultrasound criteria, neurosonography allows reliable grading of carotid stenoses as a basis for decision making.

Keywords: Carotid stenosis, ICA stenosis, Degree of stenosis, Duplex ultrasonography, Peak systolic velocity, NASCET, ECST.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S04

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Review Article

Clinical impact of Intima-Media Thickness measurement - read full article

By: Miguel Rodrigues

The Intima-Media Thickness (IMT) as measured by ultrasonography of carotid arteries is an acknowledged non-invasive method for assessing the impact of vascular risk factors and the progression of cardiovascular disease. The average of the far wall IMT of the common carotid artery (CIMT) from right and left sides is most frequently used. It correlates well with histology and it is a precursor phenotype of early atherosclerosis. Its increase is associated with vascular risk factors. Systematic reviews have quantified this risk, showing that an increase of 0.1 mm in the CIMT is associated with an increased relative risk of 8% of myocardial infarction and 12% of stroke. The evaluation of this parameter is simple, fast, and inexpensive, when integrated into a routine cervical artery ultrasound examination. However, CIMT also has applications in clinical research as an important study outcome, and then a standard measurement protocol should be applied to avoid information and measurement biases. The main consensus statements, both from Europe and North America, outline the technical conditions for IMT assessment and favor the use of automated edge detection software. The relation between CIMT and vascular risk factors or vascular events has been extensively reported. Nevertheless, the implications of CIMT change observed in repeated measurements are not so thoroughly established in the available follow-up studies. The CIMT is an attractive method of measuring target organ damage. However, it will remain a structural evaluation only, a static photograph that does not capture the complex interplay between vessel inflammation and thrombogenic processes.

Keywords: Carotid atherosclerosis, Intima-media thickness, IMT, CIMT, Cardiovascular risk assessment.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S05

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Review Article

Carotid arteries ultrasound for predicting coronary artery disease - read full article

By: Hrvoje Budincevic, Marina Milosevic, Natasa L. Andrijic, Saira A. Musemic, and Natan M. Bornstein

Ischemic heart disease and stroke are the leading causes of death in the world. Myocardial infarction or even death might be the initial presentation of ischemic heart disease. Myocardial infarction is the leading cause of long-term mortality in stroke surviving patients. The aim of this paper is to present the possibilities of predicting coronary artery disease in stroke patients. Evaluating carotid arteries intima-media thickness (IMT), plaque morphology, and degree of stenosis can give us valuable additional information for predicting cardiovascular risk and silent coronary artery disease in otherwise asymptomatic patients. Measuring IMT and assessing carotid atherosclerotic plaque is justified in subjects with high vascular risk profile.

Keywords: Coronary artery disease, Carotid artery ultrasound, Intima-media thickness, Carotid stenosis.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S06

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Review Article

Cerebral hemodynamics and the aging brain - read full article

By: Sushmita Purkayastha and Farzaneh A. Sorond

Aging is associated with a number of degenerative changes in the structure and function of blood vessels. Recent studies have examined the impact of age on cerebral hemodynamics and brain structure and function. These studies have shown age related changes in resting cerebral blood flow, cerebral vasoreactivity, cerebral autoregulation, and neurovascular coupling. Studies have also shown that aging is associated with cortical atrophy and cerebral white matter injury. More recent studies have also examined the relationship between age related cerebral hemodynamics and brain structure and function. Cross-sectional studies have shown that both cerebral vasoreactivity and pulsatility index are associated with cerebral white matter injury. Similarly, cerebral vasoreactivity has also been associated with impaired mobility which is known to be a clinical consequence of cerebral white matter injury in the elderly people. Neurovascular coupling has also been associated with slow gait and impaired executive function. Despite the advances in this field, our understanding of the relationship between cerebral hemodynamics and structural changes in the aging brain is limited. We also know very little about the relationship between cerebral hemodynamics and clinical outcomes of structural brain disease. A better understanding of these relationships is an essential step towards identifying therapeutic targets and preventive strategies for age related cerebrovascular disease. This review summarizes the available data from recent studies examining cerebral hemodynamics and the aging brain.

Keywords: Cerebral hemodynamics, Aging brain, Cerebrovascular disease, Cerebral vasoreactivity, Cerebral autoregulation, Neurovascular coupling, White matter lesions, Cognitive impairment, Cerebral blood flow.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S07

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Review Article

Multimodal brain monitoring in neurocritical care practice - read full article

By: Celeste Dias

The management of severe acute neurological patients is a constant medical challenge due to its complexity and dynamic evolution. Multimodal brain monitoring is an important tool for clinical decision at bedside. The datasets collected by the several brain monitors help to understand the physiological events of acute lesion and to define patient-specific therapeutic targets. We changed from pure neurological clinical evaluation to an era of structure and image definition associated with instrumental monitoring of pressure, flow, oxygenation, and metabolism. At each time, we want to assure perfect coupling between energy deliver and consumption, in order to ensure adequate cerebral blood flow and metabolism, avoid secondary lesion, and preserve normal tissue. Continuous monitoring of intracranial pressure, cerebral perfusion pressure, and cerebrovascular reactivity with transcranial Doppler, allows us to predict cerebral blood flow. However, adequate blood flow means not only quantity but also quality. To study and avoid tissue hypoxia we start to use methods for evaluation of oxygen extraction, such as oxygen jugular saturation, cerebral transcutaneous oximetry or measurement of oxygen pressure with intraparenchymal probes. To better understand metabolic cascade we use cerebral microdialysis to monitor tissue metabolites such as glucose, lactate/pyruvate, glycerol or cytokines involved in the acute lesion. Multimodal brain monitoring in neurocritical care practice helps neurointensivists to better understand the pathophysiology of acute brain lesion and accomplish the challenge of healing the brain and rescue lives.

Keywords: Multimodal brain monitoring, Intracranial pressure, Cerebral oximetry, Cerebral oxygenation, Cerebral blood flow, Cerebral microdialysis, Cerebrovascular reactivity indexes, Neurocritical care.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S08

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Usefulness of Doppler ultrasound in ischemic “vertigo plus” - read full article

By: J.M. de Bray, J.O. Fortrat, L. Laccoureye, and C. Verny

Vertigo is an illusion of a moving environment. Ischemic “vertigo plus” has additional focal neurological symptoms which are sometimes discrete. Before an initial Doppler examination it is possible to analyze voice, audition, gait, and wave of the hands during history taking. A patient presenting vertigo plus has to be considered as an emergency case (Stroke Unit). The following pathologies may present with symptoms of “vertigo plus": (1) Latero-medullar infarction: vertigo and a nasal voice; (2) Infarction in the posterior inferior cerebellar artery (PICA) territory—vertigo and severe ataxia and/or clumsiness of one hand; (3) Progressive infarction of the brainstem with fluctuating symptoms as vertigo, diplopia, and transient hemiparesis; (4) Infarction in the distribution of the anterior inferior cerebellar artery (AICA)—vertigo with unilateral hearing problems in 50% of the cases. With condition (1) and (2) Doppler Ultrasound (DUS) is likely to find a distal obstruction of the ipsilateral vertebral artery, with (3) and (4) a basilar artery stenosis or occlusion can be suspected and detected by DUS. In conclusion, DUS is useful in vertigo plus, especially when the hospital does not have immediate access to magnetic resonance with angio. Anyway, DUS can yield additional intracranial and cervical hemodynamic information, even after this technique.

Keywords: Vertigo, Vertebrobasilar stroke, Emergency, Doppler ultrasound, Transcranial Doppler sonography.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S09

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Original Article

Screening of cerebrovascular diseases in Stroke Prevention Centres in Latvia - read full article

By: Galina Baltgaile, Tatjana Timofejeva, Ženija Kovaldina, Anita Raita, and Jelena Pecherska

Background: To improve stroke prevention, the observation of patients suspected on having cerebrovascular disease (CVD) or stroke risk factors has been carried out in Stroke Prevention Centres (SPC) in Riga. The analysis of the incidence of CVD, correlations of clinical symptoms with diagnostic findings and risk factors was performed.

Methods: 1102 outpatients aged 7-89 years (65% female, 35 % male) underwent color- coded duplex sonography of precerebral and cerebral blood vessels (CCDS), had checked brachial blood pressure and blood test. Vascular pathology detected by CCDS was confirmed by CT angiography. Some of patients underwent X-ray, EEG, CT scan or MRI examination.

Results: Isolated dyslipidemia was the reason for observation in 2% of cases only, although 56% of surveyed had registered high level of cholesterol at the moment of observation or in the past. Patients with arterial hypertension (14% of all) had atherosclerotic lesions in arteries in 42% of cases. From 22% of patients with vertiginous syndromes and tinnitus CVD was proved in 5% of cases. Vascular pathology in cases of headache (18% of all) was found in only 11%. Silent atherosclerotic process in pre-cerebral arteries was suspected in 15% of patients but proved in 27% of all surveyed.

Conclusion: The underestimation of dyslipidemia and arterial hypertension as a stroke risk factors and the mismatch of diagnoses in patients with unspecified vestibular disorders and headache was found. The prevalence of detected silent carotid stenoses from all suspected proved the efficacy of US vascular screening in prevention, detection and follow-up of CVD.

Keywords: Stroke prevention, Stroke risk factors, Cerebrovascular diseases, Stenosis of precerebral and cerebral arteries, Vascular ultrasound screening, Vestibular disorders, Headache.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S10

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Original Article

Carotid ecodoppler and transesophageal echocardiography: complementary methods for evaluation of atherosclerosis? - read full article

By: Joana Chin, Ana Camacho, Patrícia Guilherme, Pedro Sousa, Vasco Marques, Paula Gago, Nelson Tavares, Rui Ferrinha, Sandra Cunha, Ana P. Silva, and Ilídio Jesus

Background: The purpose of this study was to assess the relationship between carotid ultrasonography (CU) and transesophageal echocardiography (TEE), regarding atherosclerotic disease findings, the presence of carotid plaques (CP), proximal aortic plaques (AP), carotid intima-media thickness (CIM), and the aortic intima-media thickness (AIM).

Methods: Sixty one patients (57.4% men, mean age 62.7 ± 14 years) were evaluated with CU and TEE with an interval inferior to one month. CIM was measured at the common carotid artery (CCA); CP was defined as a localizaed protrusion in the arterial lumen larger than 1.5 mm, in the CCA or the internal carotid, without uniform wall involvement. AIM was measured at the aortic arch; AP was defined as a hyperechogenic area with >2 mm of thickness.

Results: Thirty seven patients had CP and 19 had AP. Seventeen patients had plaques in both locations (p=0.002). There was a difference between the medians of AIM (1.4; IQR=0.5) and CIM (1.0; IQR=0.3) (p<0.001). There was a linear correlation between CIM and AIM (coef =0.378, p=0.003). The presence of CP was a predictor (OR 6.28, p=0.03) of AP. CIM (coef=0.52, p=0.05) and gender (coef=0.22, p=0.02) were predictors of AIMs.

Conclusion: The presence of CP was related to the presence of AP. There was a positive association between CIM and AIM. CU results can be used as surrogate markers of aortic atherosclerotic disease. Evaluation of thoracic aorta with TEE is important, since it provides additional information on the extent of atherosclerotic disease.

Keywords: Atherosclerosis, Transesophageal echocardiography, Carotid, Aorta, Intima-media, Plaque.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S11

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Original Article

Modifying effect of aortic atheroma on ischemic events recurrence in stroke patients with cervical and intracranial steno-occlusive disease - read full article

By: Liliana Pereira, Carina Fernandes, and Miguel Rodrigues

Background: Large artery atherosclerosis is a major cause of ischemic stroke. Ultrasound can assess aortic, supra-aortic and intracranial vessels. We describe the recurrence rate in patients with cervical/intracranial disease and aortic atheroma.

Methods: We performed a retrospective review of patients’ charts admitted to a Neurology ward with ischemic stroke/transient ischemic attack in a 5- year period. We collected clinical data, aortic, supra-aortic, and intracranial atherosclerotic changes whenever transesophageal echocardiogram was also available. Follow-up data was obtained from charts. Group comparison and recurrence risk estimates were done by Kaplan-Meier curves with Log Rank (LR) and Cox regression with Hazard Ratio (HR), with 95% confidence intervals (95% CI).

Results: Of 1300 patients, 337 underwent transesophageal echocardiogram (mean age 55.7 years; 62.9% male). Stenosis >50% or occlusion was found in 8.0% of carotid arteries, 4.2% of vertebral arteries, and 14.2% of intracranial vessels. Aortic complex plaques were found in 18.2%. Recurrence rate was 10.3% and lethality 1.3%, in 604.7 days of mean follow-up. No difference was found between risk factors of patients with or without recurrence. After 1-year of follow-up more events were seen with cervical/intracranial disease (11.7% vs 2.8%, LR p=0.006). However, cervical/intracranial disease is not predictive of recurrent events in patients without aortic atheroma (LR p=0.607), while the association is strong if aortic atheroma is present (LR p=0.013; HR=4.9; 95% CI 1.2-19.5).

Conclusion: In stroke patients investigated with transesophageal echocardiogram, cervical/intracranial disease had higher 1-year recurrence risk, but not in subjects without aortic atheroma. Presence of aortic atheroma slightly further increases recurrences.

Keywords: Ischemic stroke, Stroke recurrence, Aortic atherosclerosis, Carotid atherosclerosis, Intracranial atherosclerosis.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S12

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Original Article

Internal carotid artery stenosis: validation of Doppler velocimetric criteria - read full article

By: Ana Monteiro, Rosa Santos, Carmen Ferreira, Andreia Costa, and Elsa Azevedo

Background: Carotid endarterectomy is effective in reducing recurrent stroke in patients with carotid stenosis. Duplex sonography is widely used for diagnosing internal carotid artery (ICA) stenosis. Surgeons often base management decisions solely on this technique. Published velocimetric criteria should be validated in each laboratory. This study aims to validate Doppler velocimetric criteria for different grades of ICA stenosis and evaluate intracranial collateralization circuits.

Methods: Duplex scans from 10,435 consecutive patients routinely referred to our Neurosonology Unit from 2003 to 2011 were reviewed. Cases with ICA stenosis ?50% (ultrasonographic morphologic criteria) were grouped by percentage of stenosis (ECST method). Mean ICA peak-systolic (PSV) and end-diastolic velocities (EDV), carotid index and presence of collateral flow were recorded. Pearson’s coefficient was used to correlate percentage of stenosis and velocity parameters. One-way ANOVA was performed for the presence of collateralization.

Results: Nine-hundred and sixty cases of ICA stenosis ?50% were identified. The Pearson’s correlation values were R=0.802, p<0.001; R=0.724, p<0.001 and R=0.769, p<0.001 for the PSV, EDV and carotid index, respectively. The presence of collateral flow increased significantly for a stenosis ?70% (p<0.001). For stenosis ?70%, PSV >182 cm/s showed a sensibility of 80%, specificity of 82% and accuracy of 88%, EDV >61 cm/s showed a sensibility of 76%, specificity of 80% and accuracy of 86%, and carotid index >2.3 showed a sensibility of 82%, specificity of 82% and accuracy of 89%. These velocities were superior to the recently published consensus criteria for diagnosing stenosis ?70%. Collateral blood flow increased significantly for stenosis ?70% (p<0.001).

Conclusion: This work defined optimal velocimetric criteria for ICA stenosis in our laboratory, enabling the correct diagnosis when morphological criteria are lacking. The presence of collateralization was important to identify hemodinamically significant stenosis.

Keywords: Internal carotid artery stenosis, Velocimetric criteria, ECST, NASCET; Endarterectomy, Collateral blood flow.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S13

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Original Article

Reversal of ophthalmic artery blood flow direction and severe ipsilateral carotid stenosis - read full article

By: Miguel Grilo, Ana Monteiro, Rosa Santos, Carmen Ferreira, Andreia Costa, and Elsa Azevedo

Background: The assessment of ophthalmic artery flow direction by transcranial Doppler sonography has become part of the cerebrovascular routine examination in stroke patients. It provides helpful information for the investigation of collateral circulation and can evaluate the hemodynamic significance of high-grade internal carotid artery (ICA) stenosis. Our aim was to determine the value of assessing the direction of ophthalmic artery blood flow in the setting of routine color flow duplex ultrasonography examination of patients with ipsilateral carotid disease.

Methods: We reviewed 967 ultrasound carotid scans performed in our Neurosonology Unit from January 2003 to December 2011 with ICA stenosis ?50%, and assessed ophthalmic artery flow direction.

Results: Ophthalmic artery flow reversal was seen in 73 cases, 62 (85%) of which were in cases of ICA stenosis ?80%. Flow reversal in ophthalmic artery had a sensitivity of 43%, specificity of 99%, negative predictive value of 91% and positive predictive value of 85% for ICA stenosis ?80%.

Conclusion: We found a significant association between reversal of ophthalmic artery flow and carotid stenosis ? 80% with an excellent specificity and negative predictive value. Assessing ophthalmic artery can be especially important in patients with difficult duplex scans or with stenosis in the pre-ophthalmic artery intracranial segment of internal carotid artery, where duplex scan may fail to detect the lesion. Evaluation of ophthalmic artery blood flow direction is therefore feasible and accurate with Doppler ultrasound, and it brings very useful information to better assess intracranial hemodynamic status that can influence treatment decisions.

Keywords: Carotid stenosis, Ophthalmic artery, Reversed ophthalmic artery flow, Cerebral collateral flow pathways, Transcranial Doppler, Carotid duplex ultrasonography.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S14

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Original Article

Simulated hemodynamics in human carotid bifurcation based on Doppler ultrasound data - read full article

By: Luísa C. Sousa, Catarina F. Castro, Carlos C. António, João M.R.S. Tavares, André M.F. Santos, Rosa M. Santos, Pedro Castro, and Elsa Azevedo

Background: Atherosclerotic lesions commonly develop at arterial branch sites. Non-invasive carotid artery ultrasound is a well-established and effective method that allows real-time imaging and measurement of flow velocities. We aimed to develop a methodology for patient-specific computational 3D reconstruction and blood flow simulation based on ultrasound image data.

Methods: Subject-specific studies based on the acquisition of a set of longitudinal and sequential cross-sectional ultrasound images and Doppler velocity measurements at common carotid artery (CCA) bifurcation were performed at a university hospital. A developed simulation code of blood flow by the finite element method (FEM) that includes an adequate structured meshing of the common carotid artery bifurcation was used to investigate local flow biomechanics.

Results: Hemodynamic simulations of CCA bifurcations for six individuals were analyzed. Comparing pairs (Doppler, FEM) of velocity values, Lin’s concordance correlation coefficient analysis demonstrated an almost perfect strength of agreement (?c = 0.9911), in patients with different degrees of internal carotid artery (ICA) stenosis. Numerical simulations were able to capture areas of low wall shear stress correlated with stagnation zones.

Conclusion: Simulated hemodynamic parameters can reproduce the disturbed flow conditions at the bifurcation of CCA and proximal ICA, which play an important role in the development of local atherosclerotic plaques. This novel technology might help to understand the relationship between hemodynamic environment and carotid wall lesions, and have a future impact in carotid stenosis diagnosis and management.

Keywords: Doppler image-based analysis, Carotid bifurcation, Computational fluid dynamics, Wall shear stress.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S15

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Original Article

Transcranial color coded sonography: advanced approach using ultrasound fusion imaging - read full article

By: Stephan J. Schreiber, José M. Valdueza, and Florian Doepp

Background: Transcranial color-coded sonography (TCCS) is a well established method to study intracranial parenchymal and vascular structures. It is, however, limited by the need to insonate through available bone windows, resulting in oblique imaging planes, which can hinder easy allocation, particularly within the brain parenchyma and limit the opportunity for direct comparison with other imaging techniques. The objective of this study was to analyze the diagnostic yield of the ultrasound fusion imaging (UFI) technique using standard diagnostic approaches.

Methods: UFI is a new technique, permitting an online matching and comparison of live ultrasound images with preregistered CT or MRI images by means of a local electromagnetic field. The principles and setup of the technique for transcranial UFI is demonstrated and examples of its use in assessing established insonation planes given.

Results: UFI is suitable for transcranial insonation and allows easy combination of live ultrasound with routine diagnostic CT or MRI image datasets in the classical TCCS transtemporal and transforaminal insonation planes. System setting and matching is fast and movement artifacts are eliminated by the use of a motion tracker correction. First application in patients demonstrates easy identification and comparison of structural lesions like dilated ventricles, arachnoid cyst, or subdural hematoma.

Conclusion: UFI offers a unique opportunity to study transcranial ultrasound and CT or MRI anatomy simultaneously. It seems therefore particularly promising to be further analyzed concerning its potentials in teaching and education as well as in any intracranial condition in which repetitive intracranial imaging is required.

Keywords: Ultrasound, Virtual navigation, Transcranial color-coded sonography, Duplex ultrasound, Imaging planes.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S16

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Original Article

Clinical predictors of increased middle cerebral artery pulsatility - read full article

By: Ana Gouveia, João Sargento-Freitas, João Madaleno, Joana Penetra, Fernando Alves-Silva, Cristina Machado, Gustavo Cordeiro, and Luís Cunha

Background: Transcranial Doppler Pulsatility Index (PI) has traditionally been interpreted as a descriptor of distal cerebrovascular resistance. Many authors have investigated its usefulness in the context of traumatic brain injury (TBI), subarachnoid hemorrhage (SAH) and hydrocephalus. Nonetheless, many doubts remain about its interpretation in cerebrovascular prevention. The aim of our study is to identify the clinical predictors of increased PI.

Methods: We conducted an analysis of a prospective database including all patients undergoing cerebrovascular ultrasonographic evaluation during 2011. We excluded patients with ?70% stenosis or occlusion in any intra or extracranial artery, stenosis in middle cerebral artery (MCA), atrial fibrillation, patients without transtemporal sonographic window and all evaluations performed in context of TBI, SAH, acute ischemic stroke or intracranial hypertension. The mean PI of both MCA, measured in its middle third after a minimum of 10 minutes of rest in the supine position, was registered. Vascular risk factors and clinical conditions were analyzed.

Results: Of the 947 patients analyzed, 446 were included, of which 287 (64.3%) were male. The mean age was 62.7 years (SD = 14.92) and the mean PI was 0.995 (SD = 0.240). In multivariate analysis, age (regression coefficient Beta (B):0.007, 95% CI: 0.005-0.009, p<0.001), hypertension (B:0.056, 95% CI: 0.003-0.108, p=0.037) and diabetes mellitus (B:0.064, 95% CI: 0.006-0.121, p=0.030) were identified as predictors of increased PI.

Conclusion: These results suggest that PI is associated with vascular risk factors classically responsible for small vessel disease. We discuss the pathophysiology of elevation of PI and its possible usefulness in cerebrovascular prevention.

Keywords: Pulsatility Index, Transcranial Doppler, Cerebrovascular resistance, Small vessel disease, Cerebrovascular prevention.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S17

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Original Article

Impaired autoregulation is associated with mortality in severe cerebral diseases - read full article

By: Bernhard Schmidt, Jens J. Schwarze, Marco Weinhold, Vesna Lezaic, Marek Czosnyka, and Jürgen Klingelhöfer

Background: Small cerebral vessels respond to variations of cerebral perfusion pressure (CPP) by changes of vessel diameter inducing changes of blood flow resistance and keeping cerebral blood flow constant. This mechanism is called cerebral autoregulation (CA). An index Mx, observing correlation between cerebral blood flow velocity (CBFV) and CPP has been recently introduced for assessment of state of CA during spontaneous changes of CPP. In the current study, the relationship between lethal outcome during hospitalization and Mx index was investigated.

Methods: Thirty patients (18-77 years, mean 53±16 years) with severe cerebral diseases were studied. CBFV, arterial blood pressure (ABP,) and intracranial pressure (ICP) were simultaneously recorded. Assessments were repeated at days 2, 4 and 7. Mx was calculated retrospectively, as averaged correlation between CBFV and CPP (=ABP-ICP). Positive values of Mx indicated impairment of CA.

Results: Six of the patients died in-hospital. In this group Mx was significantly higher than in the group of survivors (0.28±0.40 versus 0.03±0.21; p<0.05). Changes of Mx during days of monitoring (Mx last day - Mx first day) were not significantly related to mortality. Nine patients showed an Mx >0.2, four of them died, whereas from the 21 patients with Mx <0.2 only two died . The association between increased Mx and death was significant (p<0.05, Fisher’s exact test). Mx correlated significantly with Glasgow Outcome Score (GOS) in the subgroup of patients with known GOS (N=21; R=-0.56, p<0.05).

Conclusion: Increased Mx indicates impairment of CA and is associated with risk of death in patients with severe cerebral diseases.

Keywords: Cerebral autoregulation, Cerebral perfusion pressure, Intracranial pressure, Cerebral disease.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S18

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Original Article

Capability of cerebral autoregulation assessment in arteriovenous malformations perinidal zone - read full article

By: Vladimir Semenyutin, Grigory Panuntsev, Vugar Aliev, Andreas Patzak, Dmitry Pechiborsch, and Alexandr Kozlov

Background: Cerebral autoregulation (CA) in the region of an intracranial artery involved in blood supply of arteriovenous malformations (AVM) is impaired. This could be due to pathologic shunting, disguising real state of CA, or brain lesion in perinidal area. It is quite difficult to define the influence of both factors on CA. The purpose of this study was to assess dynamics of CA in patients with AVM in perioperative period.

Methods: The radicality of AVM embolization (Hystoacryl or Onyx) was evaluated in 47 patients by cerebral angiography and blood flow index in precerebral arteries with a Vivid E ultrasound scanner. We monitored blood flow velocity (BFV) in basal cerebral arteries with Multi Dop X and blood pressure (BP) with Finapres-2300. CA was assessed with cuff test (autoregulation index – ARI) and phase-shift (PS) between spontaneous oscillations of BP and BFV within the range of Mayer’s waves.

Results: Preoperative values of ARI and PS were 1.8±0.7 and 0.3±0.2 rad, respectively. In 15 cases with total embolization a significant (p<0.005) increase of rate of CA (ARI: 6.0±1.1, PS: 0.9±0.1 rad) was noted. In other two cases with total embolization, CA didn’t change significantly after operation. In 14 cases with subtotal embolization postoperative ARI and PS were 3.6±0.5 and 0.7±0.1 rad, respectively (p<0.05), and in cases with partial elimination were 2.1±0.6 and 0.4±0.1 rad (p>0.05).

Conclusion: CA assessment could be used for detection of its real impairment in perinidal zone of AVM during the staged endovascular treatment and for prognostication of postoperative complications.

Keywords: Cerebral autoregulation, Cerebral blood flow volume, Arteriovenous malformation, Embolization.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S19

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Original Article

Convergent cross mapping: a promising technique for cerebral autoregulation estimation - read full article

By: Linda Heskamp, Aisha S.S. Meel-van den Abeelen, Joep Lagro, and Jurgen A.H.R. Claassen

Background: Cerebral autoregulation (CA) is the physiological mechanism that keeps the cerebral blood flow velocity (CBFV) relatively constant despite changes in arterial blood pressure (ABP). Currently, transfer function analysis (TFA) is widely used to assess CA non-invasively. TFA is based on the assumption that CA is a linear process, however, in reality CA is a non-linear process. This study explores the usability of convergent cross mapping (CCM) as a non-linear analysis technique to assess CA.

Methods: CCM determines causality between variables by investigating if historical values of a time-series X(t) can be used to predict the states of a time-series Y(t). The Pearson correlation is determined between the measured Y(t) and the predicted Y(t) and increases with increasing time-series length to converge to a plateau value. When used for CA, normal and impaired CA should be distinguishable by a different plateau value. With impaired CA, ABP will have a stronger influence on CBFV, and therefore the CBFV signal will contain more information on ABP. As a result, the correlation converges to a higher plateau value compared to normal CA. The CCM method was validated by comparing normal CA (normocapnia: breathing 0-2% CO2) with a model of impaired CA (hypercapnia: breathing 6-7% CO2).

Results: CCM correlation was higher (p=0.01) during hypercapnia (0.65 ± 0.16) compared to normocapnia (0.51 ± 0.18).

Conclusion: CCM is a promising technique for non-linear cerebral autoregulation estimation.

Keywords: Cerebral autoregulation, Convergent cross mapping, Non-linear analysis.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S20

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Original Article

Continuous monitoring of vertebrobasilar hemodynamics utilizing TCDS transducer holder Sonopod during postural changes - read full article

By: Toshiyuki Shiogai, Mayumi Yamamoto, Yuka Arima, Daichi Yamasaka, Kenji Yoshikawa, Toshiki Mizuno, and Masanori Nakagawa

Background: The objective was to evaluate continuous monitoring in the vertebrobasilar arteries (VBA), utilizing the transducer holder Sonopod for transcranial color duplex sonography (TCDS), vertebrobasilar hemodynamics and autoregulation, during postural changes.

Methods: Subjects were five normal controls and seven patients: two patients with arterial hypertension, three with dizziness (peripheral neuropathy, hepatic cirrhosis, and unknown), one with lacunar infarction and diabetes mellitus (LI/DM), and one with spino-cerebellar degeneration (SCD). TCDS utilizing the transducer holder Sonopod was used to continuously monitor the intracranial VA and BA. Blood pressure (BP), heart and respiration rates were also monitored. During two series of postural changes (supine or sitting to/from standing), a) clinical symptoms, b) BP: systolic, mean, and diastolic pressures (SBP, MBP, and DBP), c) TCDS: time-averaged maximum velocity (Vmax) and pulsatility index (PI), estimated cerebrovascular resistance (eCVR) = MBP/Vmax, and autoregulation index (ARI) = %?eCVR/%?MBP, were all calculated on the basis of maximum and minimum values during both series and of separate values from sitting to standing.

Results: a) Severe dizziness resulted in an inability to remain standing in two patients (LI/DM and SCD). b) BP: 1) ?DBP >10mmHg in all cases. 2) ?SBP>20mmHg in 2 controls and all but one patient (LI/DM). c) TCDS: 1) ?PI and ?eCVR tended to increase in the two severe dizziness patients. 2) ARI for both normal control subjects and patients fluctuated in all series and during individual standing.

Conclusion: Continuous TCDS monitoring in the VBA during postural changes is capable of evaluating vertebrobasilar autoregulation associated with autonomic regulation.

Keywords: Transcranial color duplex sonography, Transducer holder sonopod, Vertebrobasilar artery, Autoregulation, Postural changes.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S21

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Original Article

Transcranial targeting low frequency ultrasound thrombolysis system: evaluation of the probe fixation devices for blood flow monitoring - read full article

By: Jun Shimizu, Hidetaka Mitsumurab, Ayumi Arai, Jun Kubotaa, Takashi Azuma, Takeki Ogawa, and Hiroshi Furuhata

Background: We developed the transcranial targeting low frequency ultrasound thrombolysis system (TCTLoFUT) which will be used for an acute ischemic stroke (AIS). TCT-LoFUT can emit the T beam (500 kHz continuous waveform, 0.72 W/cm2) for thrombolysis to a target thrombus with the D beam (2 MHz pulsed waveform, 0.72 W/cm2) for diagnostic TC-CFI. We report the in vitro thrombolytic efficacy by TCTLoFUT and estimate the blood flow monitoring in human with a newly developed head-fixture for TCT-LoFUT using a same aspect of commercial probe.

Methods: A) Sonothrombolysis experiment: The 1.25 ml of blood was extracted by the healthy volunteer. The blood in a syringe for 40 min and created a fresh thrombus with a centrifuge (4500 rotation / 5 min). The alteplase concentration in a syringe solution was made to be 358 IU/ml. The intermittent T/D beams were applied under the 60 min of protocol which was described in our studies. The rt-PA independent group (rt-PA, n=39) and the rt-PA + TCT-LoFUT group (rt-PA+US, n=13) were compared. The sound intensity in a syringe was 0.05 W /cm2. B) Blood-flow monitoring evaluation: We evaluated the blood flow monitoring by middle cerebral artery (MCA) detection in 10 healthy volunteers for 30 min. We used the 2.5 MHz TCCFI probe with the fixture which was developed for same aspect of the TCT-LoFUT.

Results: A) Sonothrombolysis experiment: The recanalization rate of 60 min after were 64.1% in rt-PA group and 92.3% in rt-PA+US group. Average recanalization time was shortened from 27.2 min in rt-PA group to 21.4 min in rt-PA+ US group ( p < 0.01). B) Blood-flow monitoring evaluation: The MCA could be detected using the fixture for TCT-LoFUT.

Conclusion: TCT-LoFUT has a function of the blood-flow monitoring simultaneously with a thrombolysis accelerating effect which will be used for AIS patients.

Keywords: Sonothrombolysis, Low frequency, Color flow imaging, Fixation.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S22

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Original Article

Improving uniformity of intensity distribution of ultrasound passing through a human-skull fragment by random modulation - read full article

By: Osamu Saito and Hiroshi Furuhata

Background: Transcranial ultrasound irradiation can enhance the effect of a thrombolytic-agent tissue plasminogen activator (tPA), depending on the intensity. Because of the ultrasound’s interference, its intensity distribution near a transducer is not uniform, i.e., there are low-intensity cold spots and high-intensity hot spots. Furthermore, the distribution can be more inhomogeneous when the ultrasound passes through a human skull. At the cold spots, the enhancement of the tPA effect is less than in other areas, whereas at the hot spots, the risk of hemorrhages is higher. Therefore, the reduction of the difference in the intensity between the cold and hot spots, i.e., improving the uniformity of the ultrasound field, is important for effective and safer ultrasound irradiation. The purpose of this study is to show that the uniformity of the ultrasound field can be improved by random modulation of the activating signal used for the ultrasound emission.

Methods: A hydrophone measurement of the distribution of ultrasound passing through a human skull fragment in water was performed for each of the sinusoidal activations (500 kHz) and random modulation. To quantify the degree of uniformity of an intensity distribution, the term uniformity index is newly defined in this paper. This index is smaller for more homogeneous distribution.

Results: It was shown that ultrasound radiation was more homogeneous during random modulation. The uniformity index was smaller for sinusoidal activation than for random modulation in the near-field region.

Conclusion: This technique is expected to be useful for developing effective and safer therapeutic equipment.

Keywords: Sonothrombolysis, Uniformity, Random modulation, Transcranial ultrasonication.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S23

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Original Article

Collateral cerebral venous outflow by scalp veins in patients with parasagittal meningiomas - read full article

By: Vladimir Semenyutin, Dmitry Pechiborsch, Vugar Aliev, Andreas Patzak, Grigory Panuntsev, and Alexandr Kozlov

Background: Invasion of the superior sagittal sinus (SSS) by parasagittal meningiomas (PSM) causes formation of collateral pathways of venous outflow (including scalp veins) from the cranial cavity. However their importance, considering this function, is still under question. The purpose of this study was to determine the importance of scalp veins in collateral cerebral venous outflow in patients with PSM.

Methods: Eight patients with PSM (52-73 year-old) with invasion of the SSS and 4 healthy volunteers were examined, in supine position, with bilateral transcranial Doppler monitoring (MultiDop X, DWL) of blood flow velocity (BFV) in both middle cerebral arteries (MCA), and with blood pressure (BP) monitoring using photoplethysmography (Ohmeda, Finapres 2300). In patients circular compression of scalp veins with pneumatic cuff around glabella and inion during 3 minutes was performed, while in volunteers a simultaneous transient complete compression of both internal jugular veins controlled by ultrasound in B-mode (Vivid E, GE) was performed.

Results: Significant changes of BFV, pulsatility index (PI) and BP were not detected during the whole period of compression of scalp veins. These data indicate a low importance of scalp veins in collateral venous outflow from the cranial cavity. Simultaneous compression of both internal jugular veins in all 4 volunteers caused BFV decrease by 9±4% (p<0.05) and PI increase by 18±12% (p<0.05) associated presumably with intracranial hypertension and impairment of venous outflow from the cranial cavity.

Conclusion: Temporary circular compression of scalp veins in patients with invasion of the SSS does not cause impairment of venous outflow from the cranial cavity, which presumably indicates their low importance.

Keywords: Scalp veins, Cerebral venous outflow, Parasagittal meningiomas, Collateral venous pathways.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S24

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Case Report

Arteriovenous malformation in the carotid artery bifurcation as a rare cause of syncope: a case report - read full article

By: Dagmar Svackova, Jiri Neumann, Frantisek Charvat, Jiri Lacman, David Netuka, and Petra Bodnarova

Background: Arteriovenous malformation (AVM) is defined as a convolute of abnormally connected arteries and veins, where capillary bed is missing. The most common localization of AVM is intracranial. Brain malformations are about 20 times more frequent than extracerebral ones. Clinical signs depend on the localization of the malformation; besides local pain or bleeding, steal phenomenon often can be seen.

Case report: We present a case of a 61-year-old woman, who was admitted to the hospital because of recurrent syncopes. During the neurosonologic examination we could see the acceleration of blood flow in the left common carotid artery (133 cm/s), a huge convolute of the vessels in the area of its bifurcation and accelerated, low resistant flow in the origin of external carotid artery with PSV 270 cm/s and low resistance index (0.3–0.4). The changes were seen also in the venous part, with sings of arterial flow there. Magnetic resonance angiography was performed, and confirmed a large malformation in the carotid artery bifurcation (about 8 cm). The patient was sent to endovascular diagnostics and treatment; on digital subtraction angiography, a high-flow malformation of left lingual artery on the left half of the tongue was diagnosed. The selective embolization of the lingual artery by the coils was performed with very good radiologic and clinical outcome.

Conclusions: A thorough neurosonologic examination is important and can raise the suspicion of an arteriovenous malformation, as in this very unusual case.

Keywords: Ultrasound, Virtual navigation, Transcranial color-coded sonography, Duplex ultrasound, Imaging planes.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S25

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Case Report

Bilateral steno-occlusive disease of the middle cerebral artery: a case report with clinical-hemodynamic mismatch - read full article

By: Helena Rocha, Pedro Castro, Rosa Santos, Elsa Azevedo, and Marta Carvalho

Background: Bilateral steno-occlusive disease of middle cerebral artery (MCA) in young adults raises significant issues regarding etiology and treatment. The potential concomitance of hypoperfusion in the affected territories is of particular clinical relevance.

Case report: A 37-year-old man was admitted for a right MCA transient ischaemic attack. He was smoker, obese, dyslipidaemic, with previous history of heroin addiction and cured B and C hepatitis virus infections. Brain magnetic resonance and cardiac evaluation were normal. Transcranial color-coded sonography (TCCS) showed >50% proximal right MCA stenosis and distal left MCA occlusion. Treatment with aspirin and statin was started. Three months later, TCCS revealed >70% right MCA stenosis and left MCA occlusion. Selective angiography confirmed the steno-occlusive disease. Cerebrospinal fluid analysis revealed increased protein levels and a normal cell count. Corticotherapy was started, but the patient did not complied. Bilateral occlusion of MCA was noticed on TCCS, one month later, being the patient asymptomatic. Pulsed arterial spin labelling (PASL) revealed a severe decrease of cerebral blood flow in the distal part of both MCA territories.

Conclusions: The etiology of this progressive steno-occlusive disease remains unknown. Atherosclerosis may be a possible mechanism, however other potential etiologies must be considered giving the rapidly progressive character of the disorder. As it seems to be now stabilized, we wonder if it can be due to the vascular risk factors control and antithrombotic treatment or to a non-identified inflammatory monophasic cause. Serial TCCS played a major role in the assessment of disease progression.

Keywords: Progressive intracranial stenosis, Brain hypoperfusion, Transcranial color-coded sonography, Pulsed arterial spin labeling.

International Journal of Clinical Neurosciences and Mental Health 2014; 1(Suppl. 1):S26

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