Transcranial Doppler Recordings Research Articles

Monitoring cerebral autoregulation after brain injury: multimodal assessment of cerebral slow-wave oscillations using near-infrared spectroscopy.

Continuous monitoring of cerebral autoregulation might provide novel treatment targets and identify therapeutic windows after acute brain injury. Slow oscillations of cerebral hemodynamics (0.05-0.003 Hz) are visible in multimodal neuromonitoring and may be analyzed to provide novel, surrogate measures of autoregulation. Near-infrared spectroscopy (NIRS) is an optical neuromonitoring technique, which shows promise for widespread clinical applicability because it is noninvasive and easily delivered across a wide range of clinical scenarios. The aim of this study is to identify the relationship between NIRS signal oscillations and multimodal neuromonitoring, examining the utility of near infrared derived indices of cerebrovascular reactivity. Twenty-seven sedated, ventilated, brain-injured patients were included in this observational study. Intracranial pressure, transcranial Doppler-derived flow velocity in the middle cerebral artery, and ipsilateral cerebral NIRS variables were continuously monitored. Signals were compared using wavelet measures of phase and coherence to examine the spectral features involved in reactivity index calculations. Established indices of autoregulatory reserve such as the pressure reactivity index (PRx) and mean velocity index (Mx) and the NIRS indices such as total hemoglobin reactivity index (THx) and tissue oxygen reactivity index (TOx) were compared using correlation and Bland-Altman analysis. NIRS indices correlated significantly between PRx and THx (rs = 0.63, P < 0.001), PRx and TOx (r = 0.40, P = 0.04), and Mx and TOx (r = 0.61, P = 0.004) but not between Mx and THx (rs = 0.26, P = 0.28) and demonstrated wide limits between these variables: PRx and THx (bias, -0.06; 95% limits, -0.44 to 0.32) and Mx and TOx (bias, +0.15; 95% limits, -0.34 to 0.64). Analysis of slow-wave activity throughout the intracranial pressure, transcranial Doppler, and NIRS recordings revealed statistically significant interrelationships, which varied dynamically and were nonsignificant at frequencies <0.008 Hz. Although slow-wave activity in intracranial pressure, transcranial Doppler, and NIRS is significantly similar, it varies dynamically in both time and frequency, and this manifests as incomplete agreement between reactivity indices. Analysis informed by a priori knowledge of physiology underpinning NIRS variables combined with sophisticated analysis techniques has the potential to deliver noninvasive surrogate measures of autoregulation, guiding therapy.

Technical Difficulties Due to Poor Acoustic Insonation during Transcranial Doppler Recordings in Amerindians and Individuals of European Origin. A Comparative Study

Background: There is no information on transcranial Doppler (TCD) failures due to poor insonation among native inhabitants of Latin America. Methods: Seventy Ecuadorian natives and 70 age- and sex-matched individuals of European origin underwent TCD. The same investigators performed all exams using the same equipment and protocol. Using the McNemar's test for correlated proportions, we compared TCD failures related to poor insonation across ethnic groups. Results: Out of 140 participants, 56 (40%) had one or more suboptimal/absent acoustic windows. These persons were older (p = 0.01) and were more often women (p < 0.0001) than those with all optimal windows (irrespective of race/ethnicity). In the matched-pair analysis, Amerindians were more likely to have suboptimal/absent acoustic windows than individuals of European origin (OR: 2.8, 95% CI: 1.3-6.5, p = 0.006). Conclusion: Amerindians are almost three times more likely to have insonation failures related to poor acoustic windows than their European counterparts.

Cranial Accelerometry Can Detect Cerebral Vasospasm Caused by Subarachnoid Hemorrhage.

We previously reported the presence of a cranial "bruit" in patients with cerebral vasospasm by signal processing cranial accelerometry signals time locked to the cardiac cycle. This shift to higher frequencies is likely related to the turbulence of blood flow produced by vascular narrowing. We sought to build a more quantitative model to predict cerebral vasospasm then test the accuracy of this technique to detect cerebral vasospasm in a prospective blinded study. Skull accelerometry was performed using an array of 6 highly sensitive accelerometers placed in contact with the scalp. Paired transcranial Doppler (TCD) recordings and accelerometry epochs were obtained in consecutive patients with subarachnoid hemorrhage undergoing TCD recordings for surveillance of cerebral vasospasm. The energy of rectified acceleration measurements within systolic and diastolic bands of the cardiac cycle were measured and correlated with TCD-defined spasm. This model was then tested prospectively in a blinded consecutive sample of subarachnoid hemorrhage patients to determine accuracy of the technique. We developed a model predicting cerebral vasospasm from analysis of 14 unblinded subjects with varying degrees of cerebral vasospasm as detected by TCD. We then recorded from 58 subjects obtaining 125-paired recordings of accelerometry and TCD to test this model in a blinded analysis. Accelerometry detection of any spasm versus non-spasm correlated with TCD-defined vasospasm (P<0.001). The model was 81% sensitive for detecting any cerebral vasospasm in patients, while the negative predictive value was 61%. Highly sensitive skull accelerometry can detect cerebral vasospasm with clinically meaningful accuracy. This tool holds promise in the ICU environment to detect as well as reject cerebral vasospasm as the cause of neurological deficits in subarachnoid hemorrhage.

Relationship of Vascular Wall Tension and Autoregulation Following Traumatic Brain Injury

The vascular wall tension (WT) of small cerebral vessels can be quantitatively estimated through the concept of critical closing pressure (CrCP), which denotes the lower limit of arterial blood pressure (ABP), below which small cerebral arterial vessels collapse and blood flow ceases. WT can be expressed as the difference between CrCP and intracranial pressure (ICP) and represent active vasomotor tone. In this study, we investigated the association of WT and CrCP with autoregulation and outcome of a large group of patients after traumatic brain injury (TBI). We retrospectively analysed recordings of ABP, ICP and transcranial Doppler (TCD) blood flow velocity from 280 TBI patients (median age: 29 years; interquartile range: 20-43). CrCP and WT were calculated using the cerebrovascular impedance methodology. Autoregulation was assessed based on TCD-based indices, Mx and ARI. Low values of WT were found to be associated with an impaired autoregulatory capacity, signified by its correlation to FV-based indices Mx (R = -0.138; p = 0.021) and ARI (R = 0.118; p = 0.048). No relationship could be established between CrCP and any of the autoregulatory indices. Neither CrCP nor WT was found to correlate with outcome. Impaired autoregulation was found to be associated with a lower WT supporting the role of vasoparalysis in the loss of autoregulatory capacity. In contrast, no links between CrCP and autoregulation could be identified.

An analysis of cerebral blood flow from middle cerebral arteries during cognitive tasks via functional transcranial Doppler recordings

Functional transcranial Doppler (fTCD) is a useful medical imaging technique to monitor cerebral blood flow velocity (CBFV) in major cerebral arteries. In this paper, CBFV changes in the right and left middle cerebral arteries (MCA) caused by cognitive tasks, such as word generation tasks and mental rotation tasks, were examined using fTCD. CBFV recordings were collected from 20 healthy subjects (10 females, 10 males). We obtained both the raw CBFV signal and the envelope CBFV signal, which is the maximal velocity to gain more information about the changes and hemisphere lateralization in cognitive tasks compared to the resting state. Time, frequency, time–frequency, and information-theoretic features were calculated and compared. Sex effects were also taken into consideration. The results of our analysis demonstrated that the raw CBFV signal contained more descriptive information than the envelope signals. Furthermore, both types of cognitive tasks produced higher values in most signal features. Geometric tasks were more distinguished from the rest-state than verbal tasks and the lateralization was exhibited in right MCA during geometric tasks. Our results show that the raw CBFV signals provided valuable information when studying the effects of cognitive tasks and lateralization in the MCA.

Plaque at RISK (PARISK): Prospective Multicenter Study to Improve Diagnosis of High-Risk Carotid Plaques

Patients with symptomatic carotid artery stenosis are at high risk for recurrent stroke. To date, the decision to perform carotid endarterectomy in patients with a recent cerebrovascular event is mainly based on degree of stenosis of the ipsilateral carotid artery. However, additional atherosclerotic plaque characteristics might be better predictors of stroke, allowing for more precise selection of patients for carotid endarterectomy. We investigate the hypothesis that the assessment of carotid plaque characteristics with magnetic resonance imaging, multidetector-row computed tomography angiography, ultrasonography, and transcranial Doppler, either alone or in combination, may improve identification of a subgroup of patients with < 70% carotid artery stenosis with an increased risk of recurrent stroke. The Plaque At RISK (PARISK) study is a prospective multicenter cohort study of patients with recent (<3 months) neurological symptoms due to ischemia in the territory of the carotid artery and < 70% ipsilateral carotid artery stenosis who are not scheduled for carotid endarterectomy or stenting. At baseline, 300 patients will undergo magnetic resonance imaging, multidetector-row computed tomography angiography, and ultrasonography examination of the carotid arteries. In addition, magnetic resonance imaging of the brain, ambulatory transcranial Doppler recording of the middle cerebral artery and blood withdrawal will be performed. After two-years, imaging will be repeated in 150 patients. All patients undergo a follow-up brain magnetic resonance imaging, and there will be regular clinical follow-up until the end of the study. The combined primary end-point contains ipsilateral recurrent ischemic stroke or transient ischemic attack or new ipsilateral ischemic brain lesions on follow-up brain magnetic resonance imaging.

Assessment of Resting-State Blood Flow Through Anterior Cerebral Arteries Using Trans-cranial Doppler Recordings

Trans-cranial Doppler (TCD) recordings are used to monitor cerebral blood flow in the main cerebral arteries. The resting state is usually characterized by the mean velocity or the maximum Doppler shift frequency (an envelope signal) by insonating the middle cerebral arteries. In this study, we characterized cerebral blood flow in the anterior cerebral arteries. We analyzed both envelope signals and raw signals obtained from bilateral insonation. We recruited 20 healthy patients and conducted the data acquisition for 15 min. Features were extracted from the time domain, the frequency domain and the time-frequency domain. The results indicate that a gender-based statistical difference exists in the frequency and time-frequency domains. However, no handedness effect was found. In the time domain, information-theoretic features indicated that mutual dependence is higher in raw signals than in envelope signals. Finally, we concluded that insonation of the anterior cerebral arteries serves as a complement to middle cerebral artery studies. Additionally, investigation of the raw signals provided us with additional information that is not otherwise available from envelope signals. Use of direct trans-cranial Doppler raw data is therefore validated as a valuable method for characterizing the resting state.

Assessment of Reverse Flow as a Means of Cerebral Protection during Carotid Artery Stent Placement with Diffusion-weighted and Transcranial Doppler Imaging

PurposeTo assess the effectiveness of flow reversal as an alternative means of cerebral protection by using transcranial Doppler recordings and diffusion-weighted imaging (DWI) as surrogate markers of brain injury. Materials and MethodsEighteen patients with symptomatic carotid artery disease were recruited. Magnetic resonance imaging was performed before the intervention and at 3 and 24 hours and 30 days after the intervention to detect new ischemic lesions with DWI. Transcranial Doppler recordings were made during the procedure to assess for microembolic signals (MESs). Data were compared against data from a historical control cohort of patients who underwent CAS placement with or without filter protection (n = 15 each) under the same protocol in a different study. ResultsThere were fewer periprocedural new lesions on DWI in the reverse-flow cohort compared with the historical control cohort with filter protection (P = .084). Reverse flow revealed significantly fewer MESs during the whole procedure compared with the filter-protected group (P = .01) but not the unprotected group (P = .55). There was a marked decrease in MES counts for reverse flow protection during the embologenic stages of the procedure (P = .004). ConclusionsUse of the reverse flow device was associated with fewer overall lesions on DWI and proportionately fewer positive scans compared with the use of filter-type devices (P = .08, not significant). Transcranial Doppler recordings demonstrated a significant reduction in embolization to the brain during carotid artery stent placement with the use of reverse-flow cerebral protection.

An Analysis of Resting-State Functional Transcranial Doppler Recordings from Middle Cerebral Arteries

Functional transcrannial Doppler (fTCD) is used for monitoring the hemodynamics characteristics of major cerebral arteries. Its resting-state characteristics are known only when considering the maximal velocity corresponding to the highest Doppler shift (so called the envelope signals). Significantly more information about the resting-state fTCD can be gained when considering the raw cerebral blood flow velocity (CBFV) recordings. In this paper, we considered simultaneously acquired envelope and raw CBFV signals. Specifically, we collected bilateral CBFV recordings from left and right middle cerebral arteries using 20 healthy subjects (10 females). The data collection lasted for 15 minutes. The subjects were asked to remain awake, stay silent, and try to remain thought-free during the data collection. Time, frequency and time-frequency features were extracted from both the raw and the envelope CBFV signals. The effects of age, sex and body-mass index were examined on the extracted features. The results showed that the raw CBFV signals had a higher frequency content, and its temporal structures were almost uncorrelated. The information-theoretic features showed that the raw recordings from left and right middle cerebral arteries had higher content of mutual information than the envelope signals. Age and body-mass index did not have statistically significant effects on the extracted features. Sex-based differences were observed in all three domains and for both, the envelope signals and the raw CBFV signals. These findings indicate that the raw CBFV signals provide valuable information about the cerebral blood flow which can be utilized in further validation of fTCD as a clinical tool.

Abstract 53: Cerebral Hemodynamic Changes in Patients with Wartime Traumatic Brain Unjury

Cerebral vasospasm (VSP) is a frequent complication after aneurysmal and traumatic subarachnoid hemorrhage (SAH) and carries significant morbidity and mortality. Traumatic brain injury (TBI) is associated with the severest casualties from Operation Iraqi Freedom and Operation Enduring Freedom. From Oct. 1, 2008 the US Army Medical Department initiated a transcranial Doppler (TCD) ultrasound service for TBI; included patients were retrospectively evaluated for TCD-determined incidence of posttraumatic cerebral vasospasm and intracranial hypertension after wartime TBI. Patients were identified using a computerized registry and a prospective TCD database maintained in the Sentient NeuroCare Services. TCD recordings of mean cerebral blood flow velocities (CBFV) and Pulsatility Indices of the anterior and posterior circulation vessels were recorded using a 2-MHz transducer (Doppler Box, DWL/Compumedics, USA, Germany/Australia). Comprehensive TCD protocol was applied in all cases: if mean CBFV equaled or exceeded 100 cm/sec., 140 cm.sec and 200 cm/sec the TCD signs of mild vasospasm, moderate vasospasm and severe vasospasm respectively were considered present. 122 patients were investigated with daily TCD studies and comprehensive TCD protocol and published diagnostic criteria for VSP and raised intracranial pressure (ICP) were applied. TCD signs of mild, moderate and severe VSP involving anterior circulation vessels were observed in 71%, 42% and 16% of patients, respectively. TCD signs of mild, moderate and severe VSP involving posterior circulation vessels were observed in 57%, 32% and 14% of patients, respectively. TCD signs of intracranial hypertension were recorded in 43%, eight patients (7%) underwent transluminal angioplasty for post-traumatic symptomatic vasospasm treatment. These findings demonstrate that cerebral arterial VSP and intracranial hypertension are frequent and significant complications of combat TBI, therefore daily TCD monitoring is recommended for their recognition and subsequent management. Acknowledgements. The opinions and views expressed herein belong solely to those of the authors. They are not nor should they be implied as being endorsed by the Uniformed Services University of the Health Sciences, Department of the Army, Department of the Navy, Department of Defense or any other branch of the Federal government of the United States. This paper supported in part, by the US Army Medical Research and Material Command’s Telemedicine and Advanced Technology Research Center (Fort Detrick, MD, USA).

Computed Tomography and Transcranial Doppler Findings in Acute and Subacute Phases of Intracerebral Hemorrhagic Stroke

The hematoma volume is an important determinant of outcome and a predictor of clinical deterioration in patients with intracerebral hemorrhage (ICH). Our goal was to evaluate alterations in the cerebral circulation, in respect to hemorrhage and edema volume changes, using transcranial Doppler (TCD). Twenty patients with acute supratentorial ICH were examined. Brain, hematoma, and edema volumes were calculated from CT scans performed at admission and 2 weeks later. Data were compared with those obtained from bilateral TCD recordings of the middle cerebral arteries. During TCD examination, blood flow velocities did not change, cerebral perfusion pressure (CPP) and resistance area product (RAP) decreased (P = .006, P = .002) while cerebral blood flow index (CBFI) remained constant on the affected side. Although hemorrhage volume did not correlate with RAP in the acute phase, correlation was found in the subacute phase (r = -.44, P = .04). TCD monitoring sensitively demonstrates the hemodynamic change caused by ICH but the severity of the changes does not correlate with the volume of the ICH in acute stage. The CPP, RAP, and CBFI values are more sensitive parameters than the absolute velocity values, therefore they contribute more to the understanding of hemodynamic changes developed after spontaneous ICH.

妊娠14週で脳塞栓症を発症しrecombinant tissue plasminogen activator（rt-PA）静注療法を施行したプロテインS欠乏症の1例

When cerebral infarction develops during pregnancy, treatment without adverse effects must be considered not only for the mother but also for the fetus. Because pregnant women were excluded from many clinical trials, clear treatment guidance for them is not shown in the package inserts or guidelines of many drugs. We report the case of a 35-year-old woman (gravida 3, para 2) who developed sudden onset of left visual field defect, left hemiparesis, and dysesthesia over the left forearm during her fourth month of pregnancy. Brain diffusion-weighted MRI showed high intensity areas in the right occipital lobe, and magnetic resonance angiography revealed an occlusion of the right posterior cerebral artery. She was treated with an intravenous injection of recombinant tissue plasminogen activator 2 h 55 min after symptom onset, and the visual field and sensorimotor deficits improved. MRA obtained 3 days after the onset showed recanalization of the right posterior cerebral artery. We also conducted electrocardiography, neck vascular ultrasound, cardiovascular ultrasound, transcranial Doppler recordings from the temple area, and laboratory examinations for complete blood count, biochemistry, coagulation factors, endocrine secretion, and autoantibodies. Reduced protein S activity (35%) along with high intensity transient signals on transcranial Doppler indicated microemboli to be the embolic source. All other tests were negative. Anticoagulation therapy was initiated to prevent recurrence. She was initially given intravenous heparin, and then switched to warfarin therapy at 15 weeks of gestation. The patient delivered a healthy infant via caesarean section. Although reports and experiences of thrombolytic therapy with injection of recombinant tissue plasminogen activator during pregnancy remain scant, this therapy might be carefully used, especially after due consideration and understanding of the risks and benefits for both mother and fetus.

Towards increased data transmission rate for a three-class metabolic brain–computer interface based on transcranial Doppler ultrasound

In this study, we conducted an offline analysis of transcranial Doppler (TCD) ultrasound recordings to investigate potential methods for increasing data transmission rate in a TCD-based brain–computer interface. Cerebral blood flow velocity was recorded within the left and right middle cerebral arteries while nine able-bodied participants alternated between rest and two different mental activities (word generation and mental rotation). We differentiated these three states using a three-class linear discriminant analysis classifier while the duration of each state was varied between 5 and 30s. Maximum classification accuracies exceeded 70%, and data transmission rate was maximized at 1.2 bits per minute, representing a four-fold increase in data transmission rate over previous two-class analysis of TCD recordings.

The Effectiveness of Dual Antiplatelet Treatment in Acute Ischemic Stroke Patients with Intracranial Arterial Stenosis: A Subgroup Analysis of CLAIR Study

Dual antiplatelet therapy with clopidogrel and aspirin reduces the presence and number of microembolic signals in patients with large artery disease. However, whether it is effective in patients with intracranial disease alone remains uncertain. We performed a subgroup analysis of the The CLopidogrel plus Aspirin for Infarction Reduction (CLAIR in acute stroke or transient ischemic attack patients with large artery stenosis and microembolic signals) study of only patients with intracranial occlusive disease, excluding those with extra cranial disease. CLAIR was a randomized-controlled, open-label, multicenter clinical trial with blinded outcome evaluation, which recruited patients with symptoms of ischemic stroke or transient ischemic attack within seven-days of onset, with large artery stenosis verified by transcranial Doppler and carotid ultrasound, and with microembolic signals detected by transcranial Doppler recording. All patients were randomized to receive clopidogrel plus aspirin daily for seven-days (dual treatment), or aspirin alone for seven-days (monotherapy). Repeated transcranial Doppler recordings for microembolic signals were made on day one, two, and seven. This subgroup study only analyzed the patients with purely intracranial large artery disease and excluded those with extra cranial stenosis. There were 70 patients recruited with purely intracranial stenosis, 34 in the dual treatment group and 36 in the monotherapy group. The proportion of the patients with positive emboli at day seven in the dual treatment group was significantly lower than that in the monotherapy group (relative risk reduction 56·5%, 95% confidence interval 2·5-80·6; P = 0·029). The number of emboli in the dual treatment group decreased significantly at day two (P = 0·043) and day seven (P = 0·018) compared with the monotherapy group. After adjustment for the number of emboli at day one, the effect of dual treatment was still significant for the reduction of presence (relative risk reduction 56·0%; 95% confidence interval 5·4-79·6; P = 0·036) and number (adjusted mean difference -0·9; 95% confidence interval -1·5 to -0·3; P = 0·004) of positive emboli at day seven. Dual treatment with clopidogrel and aspirin for seven-days is more effective than aspirin alone to reduce microembolic signals in patients with intracranial arterial stenosis.

Vasospasm Shortens Cerebral Arterial Time Constant

Cerebrovascular time constant (τ) estimates how fast cerebral blood arrives in cerebral arterial bed after each heart stroke. We investigate the pattern of changes in τ following subarachnoid hemorrhage (SAH), with specific emphasis on the temporal profile of changes in relation to the development of cerebral vasospasm. Simultaneous recordings of arterial blood pressure (ABP) and transcranial Doppler (TCD) blood flow velocity (CBFV) in MCA were performed daily in patients after SAH. In 22 patients (10 males and 12 females; median age: 48 years, range: 34-84 years) recordings done before spasm were compared to those done during spasm. Vasospasm was confirmed with TCD (mean CBFV in MCA > 120 cm/s and Lindegaard ratio > 3). τ was estimated as a product of compliance of cerebral arteries (C (a)) and cerebrovascular resistance (CVR). C (a) and CVR were estimated using mathematical transformations of ABP and CBFV waveforms. Vasospasm caused shortening of τ on both the spastic (before: 0.20 ± 0.05 s vs. spasm: 0.14 ± 0.04 s, P < 0.0008) and contralateral side (before: 0.22 ± 0.05 s vs. spasm: 0.16 ± 0.04 s, P < 0.0008). Before TCD signs of vasospasm were detected, τ demonstrated asymmetry with lower values on ipsilateral side to aneurysm, in comparison to contralateral side (P < 0.009), Cerebral vasospasm causes shortening of τ. Shorter τ at the side of aneurysm can be observed before formal TCD signs of vasospasm are observed, therefore, potentially reducing time to escalation of treatment.

The von Willebrand Inhibitor ARC1779 Reduces Cerebral Embolization After Carotid Endarterectomy

Inhibition of von Willebrand factor offers a novel approach to prevention of stroke and myocardial ischemia but has not yet been demonstrated to show efficacy on clinically relevant end points. ARC1779 is an aptamer that inhibits the prothrombotic function of von Willebrand factor by binding to the A1 domain of von Willebrand factor and thereby blocking its interaction with glycoprotein. Phase 1 studies suggest it inhibits platelet aggregation with less increase in bleeding than conventional antiplatelet agents. The effect of ARC 1779 on cerebral emboli immediately after carotid endarterectomy was investigated in a randomized clinical trial. Patients undergoing carotid endarterectomy were randomized double-blind to ARC1779 or placebo administered intravenously. Transcranial Doppler recording, to detect cerebral embolic signals, was performed in the first 3 hours postoperatively. The primary end point was time to first embolic signals. Thirty-six patients were recruited, 18 in each arm. The Kaplan-Meier median time to first embolic signals was 83.6 minutes for ARC1779 compared with 5.5 minutes for placebo. Using Cox proportional hazards embolic signals occurred statistically significantly later on ARC1779 (P=0.007). Reduced embolic signals counts were correlated with inhibition of von Willebrand factor activity (P=0.03). Increased perioperative bleeding and anemia were seen with ARC1779. von Willebrand factor inhibition reduces thromboembolism in humans. It may play a role in treatment of stroke and myocardial ischemia. The extent to which bleeding complications occur in nonoperated patients needs to be assessed in further studies. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00742612.

Signal-to-Noise Ratio of Bilateral Nonimaging Transcranial Doppler Recordings of the Middle Cerebral Artery is not Affected by Age and Sex

Differences between transcranial Doppler ultrasonography (TCD) recordings of symmetrical vessels can show true physiologic differences, but can also be caused by measurement error and other sources of noise. The aim of this project was to assess the influence of noise on estimates of dynamic cerebral autoregulation (dCA), and of age, sex and breathing manoeuvres on the signal-to-noise ratio (SNR). Cerebral blood flow (CBF) was monitored in 30 young (<40 years) and 30 older volunteers (age >60 years) during baseline conditions, breath-holding and hyperventilation. Noise was defined as the difference between beat-to-beat values of the two mean CBF velocity (CBFV) signals. Magnitude squared coherence estimates of noise vs. ABP and ABP vs. CBFV were obtained and averaged. A similar approach was adopted for the CBFV step response. The effect of age and breathing manoeuvre on the SNR was assessed using a two-way analysis of variance (ANOVA), whilst the effect of sex was investigated using a Student’s t test. No significant differences were observed in SNR (baseline 6.07 ± 3.07 dB and 7.33 ± 3.84 dB, breath-hold: 13.53 ± 3.93 dB and 14.64 ± 4.52 dB, and hyperventilation: 14.69 ± 4.04 dB and 14.84 ± 4.05 dB) estimates between young and old groups, respectively. The use of breathing manoeuvres significantly improved the SNR ( p < 10 −4) without a significant difference between manoeuvres. Sex does not appear to have an effect on SNR ( p = 0.365). Coherence estimates were not influenced by the SNR, but significant differences were found in the amplitude of the CBFV step response. (E-mail: ek161@le.ac.uk)

The effect of blood pressure calibrations and transcranial Doppler signal loss on transfer function estimates of cerebral autoregulation

There are methodological concerns with combined use of transcranial Doppler (TCD) and Finapres to measure dynamic cerebral autoregulation. The Finapres calibration mechanism (“physiocal”) causes interruptions to blood pressure recordings. Also, TCD is subject to signal loss due to probe movement. We assessed the effects of “physiocals” and TCD signal loss on transfer function estimates in recordings of 45 healthy subjects. We added artificial “physiocals” and removed sections of TCD signal from 5 min Finapres and TCD recordings. We also compared transfer function results from 5 min time series with time series as short as 1 min. Accurate transfer function estimates can be achieved in the 0.03–0.07 Hz band using beat-by-beat data with linear interpolation, while data loss is less than 10 s. At frequencies between 0.07 and 0.5 Hz, transfer function estimates become unreliable with 5 s of data loss every 50 s. 2 s data loss only affects frequency bands above 0.15 Hz. Finally, accurate transfer function assessment of autoregulatory function can be achieved from time series as short as 1 min, although gain and coherence tend to be overestimated at higher frequencies.

Analysis of Index Modulation of Doppler Microembolic Signals Part II: In Vitro Discrimination

The purpose of this study was to validate through experiments that frequency modulation (FM) of microembolic signatures was principally due to the radiation force. Several experiments were required to prove that such a frequency modulation originates from microdisplacements induced by the radiation force acting on microbubbles. The first experiment was performed to verify that the diffraction effects due to the presence of a skull did not disturb the acoustic field appreciably and to validate that a radiation force in the brain was sufficient to create a detectable microdisplacement. A second in vitro experiment using a single gate transcranial Doppler (TCD) system was conducted to show discrimination feasibility and to check that microembolic frequency modulation signatures (FMS) and frequency modulation index (FMI) were the same as those observed in vivo and those calculated by simulation. A final in vitro experiment was performed using a multigate multichannel TCD system to confirm the second experiment by directly measuring the microdisplacement induced by the radiation force. A new parameter, to be known as the position modulation index (PMI), is proposed. We showed that the radiation force is sufficient to induce detectable microdisplacements despite the presence of the skull. We also showed that the diffraction effects due to the skull induced a decrease in the ultrasound beam of 7.6 dB. Finally, we showed by using FMI and PMI that it is possible to discriminate gaseous from formed elements (<100 microns) despite the presence of the skull. The discrimination based on the FMI is an off-line technique allowing the analysis of standard TCD recordings. However, discrimination based on the PMI requires recordings obtained exclusively from a multi-gate system. (E-mail: jean-marc.girault@univ-tours.fr)

Stroke History and Chagas Disease Are Independent Predictors of Silent Cerebral Microembolism in Patients with Congestive Heart Failure

Background: Chagas disease is endemic in South and Central America, where 18 million individuals are infected by Trypanosoma cruzi, causing congestive heart failure (CHF) and cardioembolic stroke. Transcranial Doppler (TCD) is able to detect real-time microembolic signals (MES) to the brain vessels and may represent a surrogate marker of stroke risk. We aimed to determine predictors of MES in a population of patients with CHF. Methods: Consecutive CHF patients from a university-based cardiomyopathy clinic underwent TCD recording of the middle cerebral artery for 60 min by a single investigator who was blinded to all clinical data including cardiomyopathy etiology. Predictors of MES were sought by multivariable logistic regression analysis. Results: From April 2004 to February 2009, 144 patients were studied, including 62 (44.6%) patients with Chagas disease. MES were detected in 9 (6.2%) patients and were more frequent in patients with Chagas disease than in patients with other causes of CHF (12.9 vs. 1.2%, p = 0.005). In multivariate analysis corrected for age and left-ventricular ejection fraction, predictors of MES were Chagas disease (odds ratio = 1.15, 95% confidence interval = 1.05–1.26, p = 0.004) and stroke history (odds ratio = 1.27, 95% confidence interval = 1.08–1.50, p = 0.005). Conclusions: Chagas disease and stroke history are risk factors for MES independent of cardiac disease severity. Other mechanisms besides structural cardiac disease may be operative, increasing embolic risk in Chagas disease.