TCD Data Research Articles

Event-Related Cerebral Hemodynamic Assessment of Vigilance: Evidence in Favor of a More Temporally Precise Analysis

Transcranial Doppler sonography (TCD) is a neuroergonomic measure used in research on vigilance tasks. The current study focused on eventrelated analysis of TCD data, a relatively novel analytical approach that has previously been used to reveal that brain activity increases briefly when an individual detects a critical, target stimulus. Although research suggests that this detection-related response is sensitive to fatigue and demand effects associated with vigilance, future use and interpretation of event-related TCD analyses is complicated by interstudy variability in the time course and magnitude of the detection-related response. One possibility is that previous methods may have been too temporally coarse (4-second averages), so the current study reanalyzed data from one previous event-related study – this time using narrower 2-second averages. Results indicated that 2-second averages provided more precise depiction of the detection-related response than 4-second averages. We recommend use of 2-second averages for future eventrelated CBFV research.

Prolonged Automated Robotic TCD Monitoring in Acute Severe TBI: Study Design and Rationale.

Transcranial Doppler ultrasonography (TCD) is a portable, bedside, noninvasive diagnostic tool used for the real-time assessment of cerebral hemodynamics. Despite the evident utility of TCD and the ability of this technique to function as a stethoscope to the brain, its use has been limited to specialized centers because of the dearth of technical and clinical expertise required to acquire and interpret the cerebrovascular parameters. Additionally, the conventional pragmatic episodic TCD monitoring protocols lack dynamic real-time feedback to guide time-critical clinical interventions. Fortunately, with the recent advent of automated robotic TCD technology in conjunction with the automated software for TCD data processing, we now have the technology to automatically acquire TCD data and obtain clinically relevant informationin real-time. By obviating the need for highly trained clinical personnel, this technology shows great promise toward a future of widespread noninvasive monitoring to guide clinical care in patients with acute brain injury. Here, we describe a proposal for a prospective observational multicenter clinical trial to evaluate the safety and feasibility of prolonged automated robotic TCD monitoring in patients with severe acute traumatic brain injury (TBI). We will enroll patients with severe non-penetratingTBI with concomitant invasive multimodal monitoring including, intracranial pressure, brain tissue oxygenation, and brain temperature monitoring as part of standard of care in centers with varying degrees of TCD availability and experience. Additionally, we propose to evaluate the correlation of pertinent TCD-based cerebral autoregulation indicessuch as the critical closing pressure, and the pressure reactivity index withthe brain tissue oxygenationvaluesobtained invasively. The overarching goal of this study is to establish safety and feasibility of prolonged automated TCD monitoring for patients with TBI in the intensive care unit and identify clinically meaningful and pragmatic noninvasive targets for future interventions.

Abstract 65: Intrathecal Nicardipine for Cerebral Vasospasm Post Subarachnoid Hemorrhage - A Single Center Experience

Introduction: Cerebral vasospasm leading to delayed cerebral ischemia (DCI) is one of the most significant factors impacting functional outcome in patients diagnosed with non-traumatic subarachnoid hemorrhage (SAH). Effective treatment in this setting is lacking. We now report a single center retrospective cohort experience with intrathecal (IT) Nicardipine for this indication. Methods: All patients discharged between 2013-2017 diagnosed with non-traumatic SAH, either aneurysmal or idiopathic, were included in the analysis. Demographics, risk factors, clinical courses, radiological DCI, and functional outcomes were analyzed. Results: 1,085 patients were admitted with aneurysmal (n=796) or idiopathic (n=289) SAH. The mean age was 54.5±14.1 and 67.7% were women. Low grade hemorrhage (WFNS 1) was found in 42.4%, medium (WFNS 2-3) in 26.9%, and high grade (WFNS 4-5) in 30.7%. Cerebral vasospasm was diagnosed in 36.6% of the patients, and 85.4% of those received IT Nicardipine (n=339). Only 8.4% of all patients required angiography to treat vasospasm. TCD data was available for 159 patients who received IT Nicardipine. Treatment reduced mean velocities in all arteries within one day by 15.4% on average (p<0.01). This reduction was sustained for the duration of treatment. Nineteen patients (1.8%) suffered from bacterial ventriculitis, and no statistically significant correlation was noted between IT treatment and infection (OR 1.06 95%CI[0.42-2.7]). The incidence of radiological DCI, identified by blinded assement of imaging, was 9.4% and clinical DCI was 5.7%. In this cohort, 65.5% had a favorable functional outcome (mRS≤2) at 90 days. Conclusions: In a retrospective analysis, off-label IT Nicardipine is a safe and potentially effective treatment for cerebral vasospasm and prevention of the subsequent cerebral ischemia. Being the largest of its kind, this cohort could serve as a baseline for future clinical trial designs assessing IT Nicardipine safety and efficacy in a prospective, controlled fashion.

An Educational Study Promoting the Delivery of TCD Screening in Paediatric Sickle Cell Disease: A European Multi-Centre Perspective

Background: Recent studies on the impact of migration on the geographical distribution of the HbS allele have highlighted sickle cell disease (SCD) as a global public health issue. Although considered a "rare disease" due to its global frequency in the 28 countries of the European Union, SCD is the most common genetic disease in France and the United Kingdom and its frequency is steadily rising in many other countries of central and southern Europe. At present, less than 50% of children with SCD have access to TCD screening in the USA and Europe. Most centers use the non-imaging approach, as described in the STOP trials, which is a "blind technique" where there is no guiding anatomical information and thus relies heavily on operator experience. Some centers now use imaging TCD which provides anatomical information enabling the Circle of Willis to be visualized and so facilitates identification of the basal cerebral arteries and orientation of the Doppler beam when acquiring blood velocities. The primary study objective was to determine the effectiveness of the modular training program in achieving the high level of scanning competency described in the STOP trial, irrespective of practitioner background and when using either non-imaging or imaging TCD. Methodology. The modular TCD training program was developed at the training center in London and delivered to trainees at all three centers (London-UK, Padova-Italy and Dublin, Ireland). The program comprised of a 2-day instructional course covering theory and practical aspects of TCD and incorporated significant hands-on instruction. This was followed by trainees scanning at their own hospital until they had collected a log book of at least 40 scans (within a one year period), after which a scan review and competency evaluation was performed. Results.Modular training program.Nine training courses were held (six in England, one in Ireland and two in Italy); these were attended by a total of 51 trainees (Table 1). Approximately half the trainees (45%) successfully completed the competency evaluation, 20 were still in training, two of whom had failed the assessment and eight withdrew from the program due to problems with local funding for staff or equipment. The ten trainees with an ultrasound background (clinical scientists) were able to acquire TCD skills rapidly as demonstrated by the high pass rate. The findings were more variable in the clinician group (pediatricians and nurses) with five requiring refresher courses and twelve failing to complete the minimum annual scan number (forty) due to small local sickle populations. Comparative analysis of TCD data obtained before and after training.A total of 555 patients were included in this study; 181 patients at Center 1 (52 males, mean age 7.9±3.8 (range 2-15.4 years), genotypes: 134 HbSS, 39 HbSC, 8 HbSβ thalassemia), 194 patients. Center 2 (53 males, mean age 7.4±3·2 (range 2-15.1 years), genotypes: 158 HbSS, 32 HbSC, 4 HbSβ) and 154 patients at Center 3 (50 males, mean age 6.4±3.5 (range 2-15.1 years), genotypes: 154 HbSS, 10HbSC, 16 HbSβ thalassemia). There was no significant difference in gender distribution (Chi-Square=0.313, p=0.85), but more young patients were recruited in Center 3 (ANOVA, F=8.9, p<0.001), more HbSC patients in Centers 1 and 2 and more Sβ thalassemia patients in Center 3 (Chi-Square=21.0, p<0.001).Conclusion: Diagnostic vascular ultrasound is highly operator-dependent; hence training and competency validation are essential in producing skilled TCD operators. The modular training program described here was effective in ensuring standardized TCD technique, irrespective of professional background. In this multi-center study TCD velocity measurements and STOP classification were consistent, irrespective of TCD mode and European country. We believe that this is the first modular training program that has demonstrated efficacy when delivered in different European countries. Delivery of this program in areas where TCD is under-provided will augment the number of trained TCD operators, thus facilitating access to specialist diagnostic services. This will have a significant impact on public health across Europe where SCD patients are increasing due to migration. Competency and quality assurance (QA) are important components of such a screening program; further work is in progress to develop an achievable QA program for ongoing regulation of this screening program. Disclosures Colombatti: AddMedica: Consultancy; Novartis: Consultancy; Global Blood Therapeutics: Consultancy.

DYNAMIC MODELING OF CEREBRAL HEMODYNAMICS IN THE MRI SETTING

The widespread use of magnetic resonance imaging (MRI) may offer an opportunity to evaluate cerebral hemodynamics at larger and more convenient scales. MRI also provides for the assessment of regional differences in hemodynamics within different brain regions. Our objective was to derive measures of cerebral hemodynamics (autoregulation and chemoregulation) using simultaneous recording of cardiorespiratory signals during resting state fMRI. It is hypothesis that the utilized modeling approach will be able to derive hemodynamic patterns similar to these previously described using traditional methods. Two models were designed: a single-output model defined by the global BOLD signal averaged over the entire brain, and a four-output model defined by the BOLD signal averaged over the frontal, parietal, occipital, and temporal lobes. Both models were defined by the three inputs, mean arterial blood pressure (MABP), pulse rate (PR), and end-tidal CO2 (ETCO2). Data were collected on 87 subjects (mean age 64, 56 female, 46 white, 39 black, 49 MCI). The models were considerably variable between the global and four regional BOLD signals. However, the global model for the PR and ETCO2 inputs were observed to exhibit a pattern similar to that previously reported. The model for the MABP input, unaccounted for in previous studies, exhibited a similar pattern to the putative autoregulatory response observed using TCD data. It was found that the indices derived to quantify PR reactivity was reduced in this dataset among those with MCI compared to those without MCI (global mean: normal = 0.03, MCI = −.02, p = 0.009; frontal mean: normal = 0.02, MCI = −.03, p = 0.007; parietal mean: normal = 0.02, MCI = −.01, p = 0.041; temporal mean: normal = 0.01, MCI = −.02, p = 0.053). The obtained three-input models exhibit characteristics similar to previous studies under the single-input constraint. The results suggest the potential utility of the dynamic modeling cerebral hemodynamics during rest in the MRI setting. The PR reactivity index may have clinical value in delineating individuals with increased risk for AD.

Volumetric analysis of intracranial vessels: a novel tool for evaluation of cerebral vasospasm.

Together with other diagnostic modalities, computed tomography angiography (CTA) is commonly used to indicate endovascular vasospasm treatment after subarachnoid hemorrhage (SAH), despite the fact that objective, user-independent parameters for evaluation of CTA are lacking. This exploratory study was designed to investigate whether quantification of vasospasm by automated volumetric analysis of the middle cerebral artery M1 segment from CTA data could be used as an objective parameter to indicate endovascular vasospasm treatment. We retrospectively identified SAH patients who underwent transcranial Doppler sonography (TCD), CTA, and CT perfusion (CTP), with or without subsequent endovascular treatment. We determined vessel volume/vessel length of the M1 segments from CTA data and used receiver operating characteristic curve analysis to determine the optimal threshold of vessel volume to predict vasospasm requiring endovascular treatment. In addition, blinded investigators independently analyzed TCD, CTA, and CTP data. Of 45 CTA examinations with corresponding CTP and TCD examinations (24 SAH patients), nine indicated the need for endovascular vasospasm treatment during examination. In our patients, vessel volume < 5.8µL/mm was moderately sensitive but fairly specific to detect vasospasm requiring endovascular treatment (sensitivity, 67%; specificity, 78%; negative predictive value (NPV), 89%; positive predictive value (PPV), 46%). For CTA, CTP, and TCD, we found NPVs of 96%, 92%, and 89%, PPVs of 40%, 35%, and 35%, sensitivities of 89%, 78%, and 67%, and specificities of 67%, 64%, and 69%, respectively. Vessel volumes could provide a new objective parameter for the interpretation of CTA data and could thereby improve multimodal assessment of vasospasm in SAH patients.

The Effect of Splenectomy on Development of Cerebral Vasculopathy in Children with Sickle Cell Disease

Splenic complications are often seen in pediatric patients with sickle cell disease and could lead to an increase in morbidity and mortality. The most common splenic event is acute splenic sequestration crisis (ASSC) which has been often managed with surgical splenectomy. Although splenectomy has been the treatment of choice for years, the long term complications of splenectomy on vascular events has not been broadly assessed. It has been reported that splenectomy could lead to vascular complications and increased risk of thrombosis in chronic hemolytic conditions. As it was proposed, it could be partially due to the shift form extravascular hemolysis to intravascular leading to the scavenging of nitric oxide (Kato et al, 2007). In terms of cerebral vasculopathy in children with sickle cell disease, screening is usually done by measuring blood flow velocity in the main cerebral arteries using Transcranial Doppler Ultrasonography (TCD). In 2014 Peter Soh and Abdul Siddiqui reported an increased risk of cerebrovascular complications in splenectomized patients with sickle cell disease (3), but it has not been confirmed by other publications. The aim of our study is to evaluate how splenectomy affects cerebral blood flow measured by TCD in patients with homozygous HbS. The secondary aim is to evaluate if Hydroxyurea (HU) has a protective effect on the development of cerebral vasculopathy in splenectomized patients.We performed a retrospective chart review of patients with sickle cell disease Hb SS and Hb S beta thalassemia followed at the Marian Anderson Center at St. Christopher's Hospital for Children, Philadelphia between 1999 and 2016. In the final analysis we included TCD data on 153 patients, of which 36 had undergone splenectomy. A total of 516 TCD studies were collected, of which 145 patients had a history of splenectomy. Of the 516 TCD assessments in this sample, 70 (13.6%) patients were on HU of which 21 had undergone splenectomy.Pearson correlations were calculated to explore linear associations of mean cerebral blood flow velocities (CBFV) with age at the time of TCD assessment, time since splenectomy, and TCD values. Associations of CVFV with splenectomy and with HU administration for splenectomy patients were analyzed with analysis of covariance (ANCOVA). The association of time elapsed since splenectomy to TCD measure, adjusting for age at TCD assessment, was explored with multiple linear regression models. Statistical analysis was conducted with SPSS ver. 24.0.Age at the time of TCD was significantly correlated with mean right cerebral artery (RMCA) (r = -.199, p < .001), LMCA (r = -.181, p < .001), RDICA (r = -.110, p = .047), LDICA (r = -.142, p = .01) and Basilar (r = -.186, p = < .001) velocities. Tables 1 and 2 present estimated mean TCD values (calculated adjusting for age at the time of TCD). In analysis of all TCDs, the estimated mean (RMCA) velocity was significantly higher in patients with history of splenectomy than in patients without splenectomy, (Table 1). There was also significant difference in LDICA, RDICA and right posterior cerebral artery (RPCA) velocities, all of which were higher in splenectomized patients (Table 1). When analyzing the velocities according to time since splenectomy, there were significant associations between years since splenectomy (0-5, 5-10 and >10years) and with both RMCA and LMCA abnormalities. Analysis of TCD results in splenectomized patients on HU versus non-HU, indicates all estimated mean TCDs except for RPCA, are lower for the patients on HU (Table 1), with RMCA and LMCA statistically significant.Based on our analysis we conclude that in patients with homozygous HbS disease history of surgical splenectomy increases the risk for cerebral vasculopathy. It remains unclear if cerebral vasculopathy develops as a result of splenectomy or if there is a preexisting factor leading to the development of both complications. The other important finding of our study is a protective effect of hydroxyurea on the development of cerebral vasculopathy in splenectomized patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Condition of critical pressure of cerebral microcirculatory vessel closure in the case of the injured having combined craneal and brain injury and development of intracraneal hematomas

Cerebral critical closing pressure (CrCP) is an important parameter of a microcirculation. The results of the treatment of 80 patients with severe head injury and polytrauma was studied. Depending on the presence of intracranial hemorrhages the patients were divided into 2 groups. Based on the TCD and MAP data obtained the cerebral perfusion pressure and the CrCP were calculated. The average CrCP values in each of the groups (with or without hematomas) appeared to be statistically significantly higher than a mean specified value of this index. The intergroup comparison of the CrCP showed a statistically reliable increase in its level in the 2nd group on the side of the removed hematoma as compared with opposite side (p =0,019).

Brachial-ankle pulse wave velocity and ankle-brachial index are complementary tools for transcranial Doppler ultrasonography in early diagnosis of intracranial arterial stenosis/occlusion in patients with acute ischemic stroke

The aim of this study was to explore whether brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) are suitable to serve as complementary tools for TCD in early diagnosis of intracranial arterial stenosis/occlusion in patients with acute ischemic stroke (AIS). A total of 52 patients with AIS onset and 52 age-matched healthy controls were included in this study. All participants received TCD detection, and baPWV and ABI were measured. Computed topography (CT)/magnetic resonance imaging (MRI) was applied to confirm diagnosis. TCD data from all participants was collected and reviewed to diagnose stenosis and occlusion of the major intracranial arteries. Receiver operating characteristic (ROC) analysis and logistic regression analysis were used to assess and compare the diagnostic accuracy of the various diagnostic approaches. We found that a combination of TCD with either baPWV or ABI, or a combination of the three provided a significantly higher area under the curve (AUC) in detecting stenosis or occlusion in various intracranial arteries, excluding the anterior cerebral artery (ACA), when compared to TCD alone, thereby demonstrating that these combined approaches provide improved diagnostic accuracy. In conclusion, our findings suggest that both baPWV and ABI are suitable complementary tools for TCD in early diagnosis of intracranial arterial stenosis/occlusion in AIS patients and that these combinations may assist in facilitating the diagnostic process associated with this disease.

Increased platelet activation in early symptomatic vs. asymptomatic carotid stenosis and relationship with microembolic status: results from the Platelets and Carotid Stenosis Study

Cerebral microembolic signals (MES) may predict increased stroke risk in carotid stenosis. However, the relationship between platelet counts or platelet activation status and MES in symptomatic vs. asymptomatic carotid stenosis has not been comprehensively assessed. University teaching hospitals. This prospective, pilot observational study assessed platelet counts and platelet activation status, and the relationship between platelet activation and MES in asymptomatic vs. early (≤4weeks after TIA/stroke) and late phase (≥3months) symptomatic moderate or severe (≥50%) carotid stenosis patients. Full blood count measurements were performed, and whole blood flow cytometry was used to quantify platelet surface activation marker expression (CD62P and CD63) and circulating leucocyte-platelet complexes. Bilateral simultaneous transcranial Doppler ultrasound monitoring of the middle cerebral arteries was performed for 1h to classify patients as MES positive or MES negative. Data from 31 asymptomatic patients were compared with 46 symptomatic patients in the early phase, and 35 of these patients were followed up to the late phase after symptom onset. The median platelet count (211 vs. 200×10(9) L(-1) ; P=0.03) and the median percentage of lymphocyte-platelet complexes was higher in early symptomatic than asymptomatic patients (2.8 vs. 2.4%; P=0.001). The percentage of lymphocyte-platelet complexes was higher in early symptomatic than in asymptomatic patients with ≥70% carotid stenosis (P=0.0005) and symptomatic patients recruited within 7days of symptom onset (P=0.028). Complete TCD data were available in 25 asymptomatic, 31 early phase symptomatic and 27 late phase symptomatic patients. Twelve per cent of asymptomatic vs. 32% of early phase symptomatic (P=0.02) and 19% of late phase symptomatic patients (P=0.2) were MES positive. Early symptomatic MES-negative patients had a higher percentage of lymphocyte-platelet complexes than asymptomatic MES-negative patients (2.8 vs. 2.3%; P=0.0085). Recently, symptomatic carotid stenosis patients have had higher platelet counts (potentially reflecting increased platelet production, mobilization or reduced clearance) and platelet activation status than asymptomatic patients. MES were more frequently detected in early symptomatic than asymptomatic patients, but the differences between late symptomatic and asymptomatic groups were not significant. Increased lymphocyte-platelet complex formation in recently symptomatic vs. asymptomatic MES-negative patients indicates enhanced platelet activation in this early symptomatic subgroup. Platelet biomarkers, in combination with TCD, have the potential to aid risk-stratification in asymptomatic and symptomatic carotid stenosis patients.

Thermal Conductivity Detector for Gas Chromatography: Very Wide Gain Range Acquisition System and Experimental Measurements

The aim of this paper is to present an acquisition system featuring a very wide gain range and experimental measurements of a new micromachined thermal conductivity detector ( $\mu$ TCD), applied downstream of a gas-chromatography (GC) system. We describe a simple and innovative electronics for $\mu$ TCD control and data acquisition, outlining its resistance control, native imbalance compensation, and automatic gain control (AGC) algorithm. The acquisition electronics features two parallel amplification stages with programmable gain: a high-gain stage (gain: 70–1280) and a low-gain or attenuating stage (gain: 0.6–30). The resulting detection range turns out to be very wide, with full scales ranging between 3.9 mV and 6.5 V while voltage is acquired with a 10-b-resolution analog-to-digital converter. Measurements and sensitivity tests have been carried out by connecting our $\mu$ TCD and acquisition system downstream of the microfluidic section and GC column of a commercial GC system. Sensitivity measurements on several toluene masses gave very good results, having observed a system sensitivity of $15.2 \pm 0.6 \mu\hbox{Vs/ng}$ . This high sensitivity will enable the $\mu$ TCD to be used in many portable applications like in-line quality control, and industrial security and safety. We also show the good operation of the AGC algorithm.

Image guidance to improve reliability and data integrity of transcranial Doppler sonography

BackgroundPrinciples and accuracy of image-guided transcranial Doppler (IG TCD) sonography have been published recently. However, it remains open whether combination of image guidance and TCD offers an additional clinical advantage. This study scores the accuracy of conventional TCD examinations and investigates the potential improvement of TCD data integrity and reliability regarding the additional use of IG. MethodsConventional TCD was performed by a group of experienced investigators, who were blinded to images of a navigation system tracking the Doppler probe, whereas an independent observer documented the TCD findings, acquired by the investigators, due to saving spatial data of the TCD sample volume using IG for subsequent analysis. In a second set of experiments, image guidance was available to investigators without any previous TCD experience. ResultsThe analysis of 3D data of vessels (n=173) labeled by experienced investigators in conventional TCD, revealed a rate of 37% misinterpreted Doppler signals regarding the target vessel. Correctness of labeling was comparable between the different vascular segments. The rate of correct labeling was higher for right- (69%) than for left-sided vessels (57%). In comparison, by using IG, TCD investigators without any previous TCD experience achieved a significantly lower rate of 10% (n=39) mislabeled vessels. ConclusionsOur data suggest, that misinterpretation of the vascular source of the Doppler signal is a common source of errors in conventional TCD. Visualization of the vascular anatomy by image guidance offers improved accuracy and reliability of TCD results and may positively influence the learning curve for inexperienced investigators.

Cerebral vasospasm following temporal lobe epilepsy surgery

Selective amygdalohippocampectomy (AHE) has been associated with postoperative cerebral vasospasm (CVS) in patients with medically intractable temporal lobe epilepsy. The incidence in temporal lobe resection (TLR) is unknown. This retrospective cohort study evaluates the incidence of and risk factors for the development of CVS in patients with TLR and AHE. A total of 119 patients were included between 1998 and 2009. All patients were evaluated by standardized preoperative and postoperative transcranial Doppler sonography (TCD) evaluations and neurologic examinations. Postoperative CT scans were evaluated by an independent radiologist and the volume of bleeding within the resection cavity was quantified. Of 107 patients with longitudinal TCD data, 35 (32.7%) developed postoperative CVS. The incidence of CVS did not differ between patients with TLR and AHE. CVS was associated with female gender and a higher bleeding volume in the postoperative CT scan (p = 0.035 and 0.046). Patients with CVS showed a significantly higher incidence of postoperative neurologic signs and symptoms (48.6%) compared to patients without CVS (25%, p = 0.015). The mean length of stay was significantly prolonged in patients with diffuse CVS compared to patients with localized CVS or no CVS (28.8 ± 10.9, 24.2 ± 6.6, and 18.2 ± 6.1 days, p < 0.001). CVS is a frequent complication of surgery for temporal lobe epilepsy irrespective of the resection method. Important risk factors for the development of postoperative CVS are female gender and a higher amount of bleeding in the postoperative CT. Patients with CVS more frequently have neurologic signs and symptoms resulting in prolonged hospital stay.

Problems with implementing a Standardised TCD Screening Program: Impact of TCD Instrumentation Variation on STOP Classification

AbstractAbstract 2663The STOP trial provided conclusive, level 1 evidence that TCD screening reduces the risk of stroke in patients with homozygous S sickle cell disease. These findings were based on data collected from a discrete population of children in the United States using standardised non-imaging TCD instrumentation and a strict protocol for TCD data acquisition and interpretation. Since this time there has been considerable energy addressed to provide a TCD screening service to all children with SCD. Initial efforts were hampered by a lack of available TCD equipment and lack of technical expertise in TCD scanning. A solution to both problems was provided by duplex colour mapping systems which have facilitated the widespread propagation of TCD surveillance programmes. There was initial caution in the substitution of imaging TCD in the sickle surveillance programme, particular in view of the recognised differences in velocities acquired by the two TCD techniques. A number of elegant studies have been undertaken to establish the variance between the techniques and adjustments to imaging TCD diagnostic thresholds have been advised. Surveillance is now being undertaken with a range of TCD imaging systems. The present study reviewed the screening program at our institution where STOP classification is based on imaging and non-imaging TCD. Method:Data from previous comparative studies have indicated that TCD imaging velocities, obtained with a rigorous protocol, underestimate non-imaging TCD by 10%. Based on these findings a 10% adjustment was applied to the STOP thresholds. TCD imaging time-averaged maximum (TAMX) velocity data was therefore classified as normal if velocities were <155cm/s; conditional for velocities of 155–179cm/s and abnormal for >180cm/s velocities. Children seen in a One Stop clinic were first scanned with imaging TCD (Philips IU22) and those who had velocities falling in the conditional or abnormal ranges were rescanned with non-imaging TCD (Nicolet, Companion III). Results:Based on imaging-TCD velocities, 3 middle cerebral arteries were classified as abnormal, 7 conditional and the remaining 4 normal. However, repeat scanning with non-imaging TCD demonstrated; no abnormal classifications, 3 conditional and 11 normal. Comparison of TAMX velocities obtained by the two techniques showed no systematic difference (mean 1±8cm/s). Conclusion:The TCD imaging system used in this study did not demonstrate any systematic difference in velocity compared to non-imaging TCD. Reported differences in velocities between the two techniques have been attributed to manufacturer derived and technical expertise factors consequently, current STOP thresholds for imaging TCD are flawed. All centres should evaluate their imaging TCD velocities against expert derived non-imaging TCD values to determine the correct STOP velocity thresholds for their institution. Disclosures:No relevant conflicts of interest to declare.

Narrowing of the Middle Cerebral Artery: Artificial Intelligence Methods and Comparison of Transcranial Color Coded Duplex Sonography with Conventional TCD

The goal of the study was to compare performances of transcranial color-coded duplex sonography (TCCS) and transcranial Doppler sonography (TCD) in the diagnosis of the middle cerebral artery (MCA) narrowing in the same population of patients using statistical and nonstatistical intelligent models for data analysis. We prospectively collected data from 179 consecutive routine digital subtraction angiography (DSA) procedures performed in 111 patients (mean age 54.17 ± 14.4 years; 59 women, 52 men) who underwent TCD and TCCS examinations simultaneously. Each patient was examined independently using both ultrasound techniques, 267 M1 segments of MCA were assessed and narrowings were classified as ≤50% and >50% lumen reduction. Diagnostic performance was estimated by two statistical and two artificial neural networks (ANN) classification methods. Separate models were constructed for the TCD and TCCS sonographic data, as well as for detection of “any narrowing” and “severe narrowing” of the MCA. Input for each classifier consisted of the peak-systolic, mean and end-diastolic velocities measured with each sonographic method; the output was MCA narrowing. Arterial narrowings less or equal 50% of lumen reduction were found in 55 and >50% narrowings in 26 out of 267 arteries, as indicated by DSA. In the category of “any narrowing” the rate of correct assignment by all models was 82% to 83% for TCCS and 79% to 81% for TCD. In the diagnosis of >50% narrowing the overall classification accuracy remained in the range of 89% to 90% for TCCS data and 90% to 91% for TCD data. For the diagnosis of any narrowing, the sensitivity of the TCCS was significantly higher than that of the TCD, while for diagnosis of >50% MCA narrowing, sensitivity of the TCCS was similar to sensitivity of the TCD. Our study showed that TCCS outperforms conventional TCD in detection of ≤50% MCA narrowing, whereas no significant difference in accuracy between both methods was found in the diagnosis of >50% MCA narrowing. (E-mail: jaroslaw.krejza@uphs.upenn.edu)

Normal Blood Flow Velocities of Basal Cerebral Arteries Decrease with Advancing Age: A Transcranial Doppler Sonography Study

Transcranial Doppler sonography (TCD) is a non-invasive diagnostic tool enabling evaluation of blood flow characteristics of basal intracerebral vessels via thin calvarian regions. Several factors may affect the normal values of cerebral hemodynamic parameters, and standard reference values for each laboratory are needed for precise interpretation of the results. The aims of this study were to determine normal values of flow velocities of basal cerebral arteries of our TCD laboratory, and to study the influence of age and gender on normal values. We studied 63 healthy volunteers (30 male and 33 females; age range, 5 - 69 years old) with TCD with a 2-MHz transcranial probe. The subjects were divided into 7 age groups: 5-10 years, 11-20 years, 21-30 years, 31-40 years, 41-50 years, 51-60 years and > 60 years. Mean velocity (V mean), peak systolic velocity (PSV), and end-diastolic velocities (EDV) were determined in middle, anterior and posterior cerebral arteries. No significant gender difference was found. However, there was a decrease in blood flow velocities in all vessels with advancing age, which was significant when subjects older than 40 years and < or = 40 years old were compared. V mean, PSV and EDV values were highest in the age group of 5 - 10 years old and lowest in volunteers older than the age of 60 (p < 0.05). As a conclusion, flow velocities in basal cerebral arteries range widely and are significantly age-related. Age matching of TCD data is a requirement for clinically relevant conclusions.

Alpha Thalassemia is associated with decreased risk of abnormal transcranial Doppler ultrasonography in children with sickle cell anemia.

Cerebrovascular complications of sickle cell disease (SCD) are common, but the risk factors remain unclear. The multicenter Stroke Prevention Trial in Sickle Cell Anemia (STOP) provided an opportunity to examine alpha thalassemia-2 as a modifying risk factor, using abnormal transcranial Doppler ultrasonography (TCD) as a surrogate marker for cerebrovascular disease. The authors hypothesized that children with abnormal TCD are less likely to have alpha thalassemia-2, and an increased hemoglobin level accounts for this protective effect. A retrospective study was conducted of children with SCD who had both alpha gene and TCD data from STOP: 128 with TCD of at least 200 cm/s (abnormal TCD) and 172 with TCD less than 170 cm/s (normal TCD). Alpha thalassemia-2 was more frequent in the normal TCD group compared with the abnormal TCD group. The odds ratio for normal TCD and alpha thalassemia-2 was 4.1. Adjusting for either hemoglobin level or red cell size (mean corpuscular volume) reduced the odds ratio only slightly. Age, normal TCD, and alpha thalassemia-2 had significant statistical interaction, so that alpha thalassemia-2 was not related to TCD for age 10 years or older. The frequency of alpha thalassemia-2 was significantly higher in children with normal TCD. Speculation on mechanisms of effect includes improved erythrocyte deformability, reduced red cell adhesion, and reduced nitric oxide scavenging in alpha thalassemia-2. The association of alpha thalassemia-2 and normal TCD adds to the evidence on the protective effects of alpha thalassemia-2 in SCD and highlights the contribution of epistatic factors.

Ultraschalldiagnostik der intra-kraniellen Hirnarterien und Monitoring-Techniken

There have been significant further developments in ultrasound diagnostics of the intracranial brain arteries in recent years. Besides the traditional transcranial Doppler sonography (TCD) the two-dimensional colour duplex technique (TCCS) has become a well-established method. This enables a safe differentiation of the basal brain arteries even without compression tests, as well as a clear definition against surrounding parenchymal structures. It is now possible to obtain safe and rapid information on the vascular status for immediate diagnosis in brain infarction patients. Since information on vascular malformations and aneurysms can be obtained only if the vascular pathology is sufficiently large, TCCS cannot replace other methods of identification as far as this aspect is concerned. The ultrasound contrast media for whom the lungs are patent greatly improve the signal-to-noise ratio of the Doppler signal. After enhancement by the ultrasound contrast media, Doppler signals may be analysed even under unfavourable conditions (for example: insufficient penetration of sound through the temporal bone). By means of haemodynamic TCD monitoring it is now possible to determine significant characteristics of brain blood supply with relatively little effort, such as changes in the median speed of flow, cerebrovascular resistance and autoregulation. The clinical application of this kind of monitoring is demonstrated by three examples. During the interventional neuroradiological experimental occlusion of the internal carotid artery the TCD data can be used to assess haemodynamic and possible clinical effects of such an occlusion. In the tilting-table test ICD can supply valuable insights into the cerebral effects of systemic dysregulations. In a subgroup of patients with orthostatic intolerance it was only TCD that showed clear pathological changes. For practical reasons it has not yet been possible to establish TCD monitoring in continuous control checking in stroke units. However, first experiences seem to point out that possibly TCD monitoring may reveal the development for critical cerebral circulatory disturbances in patients with space-occupying media infarctions and may thus supply a significant contribution to the indication for cranial decompression. By means of repeat examinations of the course, using the TCD and TTCS technique, it is possible to identify in patients with acute cerebral infarction the time of rechannelling and to estimate the space-occupying effect of an infarction by measuring the displacement of the third ventricle. Monitoring patients after thrombendarterectomy of the internal syndrome, whereas monitoring of an embolism helps to estimate the risk of a post-operative ischaemic event.

Transcranial Doppler ultrasound criteria for hemodynamically significant internal carotid artery stenosis based on residual lumen diameter calculated from en bloc endarterectomy specimens.

Transcranial Doppler (TCD) is often used in conjunction with carotid duplex ultrasonography (CDUS) to evaluate the hemodynamic significance of internal carotid artery (ICA) stenosis. We examined the sensitivity and specificity of TCD criteria for detection of a hemodynamically significant stenosis (residual lumen diameter < 1.5 mm) at the origin of the ICA. We selected patients who underwent carotid end-arterectomy (CEA) and had preoperative TCD data available. Eighty-one patients underwent transorbital evaluation, 49 of whom also had transtemporal TCD performed. The endarterectomy specimens were removed en bloc and sectioned, and the minimal residual lumen diameter calculated by computer analysis. For the transorbital approach, the strongest indicators of a residual lumen diameter < 1.5 mm were reversed flow in the ipsilateral ophthalmic artery and a > 50% peak systolic velocity difference between the carotid siphons (distal ICAs) in patients with unilateral ICA origin stenosis. They were 100% specific and 31% and 26% sensitive, respectively. For the transtemporal approach in patients with a unilateral stenosis, a > 35% difference in ipsilateral middle cerebral artery (MCA) peak systolic velocity relative to the contralateral MCA or a > 50% difference in contralateral anterior cerebral artery (ACA) peak systolic velocity relative to the ipsilateral ACA were 100% specific for identifying a residual lumen diameter of < 1.5 mm. Sensitivities were 32% and 43%, respectively. Irrespective of contralateral stenosis, a > 35% difference in ipsilateral MCA peak systolic velocity relative to the ipsilateral posterior cerebral artery had a 100% specificity and a 23% sensitivity for detecting a < 1.5 mm minimal residual lumen diameter. Although the TCD sensitivity for detecting a hemodynamically significant stenosis is relatively low, it can be highly specific (up to 100%). We conclude that TCD enhances the specificity of highly sensitive CDUS criteria for detecting a hemodynamically significant ICA stenosis.

Effect of Pco 2 Changes Induced by Head-Upright Tilt on Transcranial Doppler Recordings

Transcranial Doppler (TCD) monitoring of mean blood flow velocity (mV) during head-upright tilt can allow testing of cerebral autoregulation. Nonetheless, head-upright tilt can induce changes in the ventilation-perfusion relationship and/or respiratory activity that might influence TCD data. Forty-eight healthy volunteers underwent monitoring of mV and end-tidal CO2 in the horizontal position and during head-upright tilt. Both mV and end-tidal CO2 significantly decreased in orthostasis (P < .01). Linear regression analysis showed a significant linkage between end-tidal CO2 and mV changes (r = .83, P < .01). Changes in ventilation-perfusion ratio and in the respiratory pattern induced by head-upright tilt can significantly influence TCD data by determining a PCO2 decrease.