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Background and Purpose— In patients with mild to moderate symptomatic carotid artery stenosis, intraplaque hemorrhage (IPH) and a thin/ruptured fibrous cap (FC) as evaluated with MRI, and the presence of microembolic signals (MESs) as detected with transcranial Doppler, are associated with an increased risk of a (recurrent) stroke. The objective of the present study is to determine whether the prevalence of MES differs in patients with and without IPH and thin/ruptured FC, and patients with only a thin/ruptured FC without IPH. Methods— In this multicenter, diagnostic cohort study, patients with recent transient ischemic attack or minor stroke in the carotid territory and an ipsilateral mild to moderate carotid artery plaque were included. IPH and FC status were dichotomously scored. Analysis of transcranial Doppler data was done blinded for the MRI results. Differences between groups were analyzed with Fisher exact test. Results— A total of 113 patients were included. Transcranial Doppler measurements were feasible in 105 patients (average recording time, 219 minutes). A total of 26 MESs were detected in 8 of 105 patients. In 44 of 105 plaques IPH was present. In 92 of 105 plaques FC status was assessable, 36 of these had a thin/ruptured FC. No significant difference in the prevalence of MES between patients with and without IPH ( P =0.46) or with thick versus thin/ruptured FC ( P =0.48) was found. Conclusions— In patients with a symptomatic mild to moderate carotid artery stenosis, IPH and FC status are not associated with MES. This suggests that MRI and transcranial Doppler provide different information on plaque vulnerability. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01709045.

Object The aim of the present study was to evaluate the time course for cerebral autoregulation (AR) recovery following severe traumatic brain injury (TBI) Methods Thirty-six patients (27 males and 9 females, mean ± SEM age 33 ± 15.1 years) with severe TBI underwent serial dynamic AR studies with leg cuff deflation as a stimulus, until recovery of the AR responses was measured. Results The AR was impaired (AR index < 2.8) in 30 (83%) of 36 patients on Days 3–5 after injury, and in 19 individuals (53%) impairments were found on Days 9–11 after the injury. Nine (25%) of 36 patients exhibited a poor AR response (AR index < 1) on postinjury Days 12–14, which eventually recovered on Days 15–23. Fifty-eight percent of the patients with a Glasgow Coma Scale score of 3–5, 50% of those with diffuse brain injury, 54% of those with elevated intracranial pressure, and 40% of those with poor outcome had no AR recovery in the first 11 days after injury. Conclusions Autoregulation recovery after severe TBI can be delayed, and failure to recover during the 2nd week after injury occurs mainly in patients with a lower Glasgow Coma Scale score, diffuse brain injury, elevated ICP, or unfavorable outcome. The finding suggests that perfusion pressure management should be considered in some of the patients for a period of at least 2 weeks.

Ten patients with mitral stenosis, but without mitral insufficiency, have been studied during cardiac catheterization. The mitral orifice blood velocities, the mitral pressure gradient, and the mitral flow rate were determined with ultrasound, manometry, and the direct Fick method, respectively. The effective orifice area was calculated from the ultrasound data and the mitral flow rate. The geometric orifice area was calculated from the pressure gradient and the mitral flow rate, using a revised Gorlin formula. A comparison of the two methods showed a correlation coefficient of 0.975. The investigation demonstrated that the ultrasound method represents an alternative to the conventional catheterization methods used for the quantification of mitral flow obstruction.

Background and Purpose— Transcranial Doppler (TCD) ultrasound can detect asymptomatic emboli in carotid stenosis. Current systems are nonportable and can only record for short durations. A novel ambulatory TCD system allows prolonged recording. We applied this to patients with symptomatic and asymptomatic carotid stenosis to determine patterns of embolization in the 2 conditions and optimal recording protocols. Methods— Ambulatory TCD recordings were performed in 12 symptomatic and 15 asymptomatic carotid stenosis (≥50%) patients for 8 hours and then repeated on a second occasion. Results— Nine (75%) of symptomatic subjects had embolic signals during the first recording. In this group, repeating the recording did not increase the proportion of positive patients. In asymptomatic patients, 4 (26.7%) had embolic signals on 1 recording, and this proportion increased to 46.7% after 2 recordings. There was significant clustering of embolic signals demonstrating that the process was nonrandom. Conclusions— Ambulatory TCD is possible in patients with carotid artery stenosis. By increasing the duration of recording, additional information is provided, particularly in asymptomatic patients. Our results also demonstrate clustering of embolic signals. Our study provides baseline data to allow studies in both asymptomatic and symptomatic carotid stenosis to be planned.

Background and Purpose— Transcranial Doppler (TCD) monitoring for asymptomatic cerebral emboli is currently limited to short recordings by equipment size, restricting its clinical usefulness. We have developed a first ambulatory TCD system, evaluated it in at-risk patient groups, and used it to study the pattern of embolization in patients with symptomatic carotid stenosis. Methods— The system comprises an 18×11.5×3.2 cm battery-powered Doppler unit (425 g) and a 13-mm servo-controlled 2 MHz transducer probe. The quadrature raw Doppler signal is stored on flash-disk. An autosearch algorithm restores vessel insonation should signal quality fall. Initial evaluation was in 20 ambulatory stroke patients. Subsequently, 12 recently symptomatic carotid patients had recordings for ≥5 hours. Results— Recordings were well tolerated and a median of 96% of Doppler signal was suitable for analysis. Embolic signals were detected in 11 of the 12 symptomatic carotid patients. There was marked temporal variability in embolization and prolonging the recording increased the yield of embolic signal positive patients from 58% at 30 minutes to 92% at 150 minutes. In 3 subjects with frequent embolic signals, significant temporal clustering of embolic signals was observed. Conclusions— We have developed the first ambulatory TCD system. Good-quality recordings of ≥5 hours can be obtained. In view of the demonstrated temporal variability in embolization, this technique is likely to improve the predictive value of recording for asymptomatic embolic signals and may be particularly useful in patients in whom embolic signals are relatively infrequent, such as those with asymptomatic carotid stenosis and atrial fibrillation.

Background and Purpose— The pressure–flow velocity relationship in the cerebral circulation is characterized by the critical closing pressure (CCP), which is the pressure at which flow ceases, and the linear slope of a plot between pressure and flow velocity. It has been suggested, but not validated, that CCP can be determined from arterial blood pressure (ABP) and transcranial Doppler (TCD) recordings during the cardiac cycle. We studied a group of patients in whom ventricular fibrillation (VF) was induced. The time interval before defibrillation enabled calculation of CCP from data in which flow approached zero. These estimates were compared with values calculated before and after fibrillation and during regular heartbeats. Methods— TCD velocities and ABP in the radial artery were recorded before, during, and after 28 episodes of VF in 13 patients. CCPs were calculated by 3 different methods: (1) linear extrapolation from data during VF (gold standard); (2) linear extrapolation from normal heartbeat data; and (3) first harmonic Fourier filtering of normal heartbeat data. Results— The CCP during VF calculated from long diastoles was 32.9±11 mm Hg (mean±SD). The regular heartbeat estimate was 6.0±4.3 mm Hg lower ( P P =NS) lower than during VF. During hyperemia after defibrillation, the CCP decreased by 13.3 mm Hg, while velocity increased by 63%. The decrease in CCP could explain half of the increase in flow velocity during hyperemia. Conclusions— CCP can be accurately estimated from regular heartbeat data and is an important factor in regulation of the cerebral circulation.

More than one-third of patients diagnosed with head injury are intoxicated with ethanol. Most clinical and animal studies have shown alcohol to have a deleterious impact in the setting of cerebrovascular trauma; however, there are also data showing neuroprotective effects in low ethanol doses. Human studies using imaging modalities suggest that small doses of alcohol produce cerebral vasodilatation and higher doses cerebral vasoconstriction. The aim of this study was to investigate the effect of ethanol intake on dynamic cerebral autoregulation and velocities in the middle cerebral arteries, and compare these changes with the effects of hypercapnia. Dynamic cerebral autoregulation and cerebral blood flow velocities were analysed before and after alcohol intake (1.1 g/kg of body weight) in six adult volunteers. Cerebral blood flow velocities in both middle cerebral arteries were monitored continuously by transcranial Doppler. A value for dynamic cerebral autoregulation was calculated from the rate of increase in middle cerebral artery velocities after a rapid-step decrease in arterial blood pressure. A sudden decrease in blood pressure was achieved by the release of previously inflated large blood pressure cuffs around the subject's thighs. Three volunteers were also tested before alcohol intake with CO(2) challenge (breathing 6% CO(2)) during the autoregulation procedure. Blood alcohol level reached 90 mg/dl approximately 60 min after ethanol ingestion. Cerebral blood velocities increased by 8% from baseline for uncorrected end-tidal (et) CO(2) and by 24% for correction to et CO(2)=40. Dynamic cerebral autoregulation measured as an autoregulation index decreased from 4.3+/-1.3 to 2.9+/-1.1 (p=0.089), which did not reach statistical significance. During hypercapnic conditions, dynamic cerebral autoregulation dropped from 4+/-0.8 to 0.9+/-0.9. In conclusion, mild alcohol intoxication caused cerebral vasodilatation with a subsequent increase in cerebral blood flow of 8-24%. Dynamic cerebral autoregulation was not found to be significantly impaired by ethanol. Hypercapnia almost completely destroys the physiological autoregulatory mechanism. A mild hyper-ventilation to etCO(2)=34-36 may be a compensatory contra-measure for ethanol-induced vasodilatation in the setting of head trauma.

Background: There is little information on the limits of cerebral autoregulation and the autoregulatory capacity in children. The aim of this study was to compare dynamic cerebral autoregulation between healthy adolescents and adults. Methods: Seventeen healthy volunteers 12–17 years (n = 8) and 25–45 years (n = 9) were enrolled in this study. Bilateral mean middle cerebral artery flow velocities (Vmca; (cm/s)) were measured using transcranial Doppler ultrasonography (TCD). Mean arterial blood pressure (MAP) and end-tidal carbon dioxide were measured continuously during dynamic cerebral autoregulation studies. Blood pressure cuffs were placed around both thighs and inflated to 30 mmHg above the systolic blood pressure for 3 min and then rapidly deflated, resulting in transient systemic hypotension. The change of Vmca to change in MAP constitutes the autoregulatory response, and the speed of this response was quantified using computer model parameter estimation. The dynamic autoregulatory index (ARI) was averaged between the two sides. Results: Adolescents had significantly lower ARI (3.9 ± 2.1 vs. 5.3 ± 0.8; P=0.05), and higher Vmca (75.2 ± 15.2 vs. 57.6 ± 15.0; P

The purpose of the study contained herein was to investigate the effects of old traditional physiotherapeutic treatments on cerebral autoregulation. Treatment consisted of complete body immersion in cold or warm water baths. Fifteen volunteers were investigated by means of transcranial Doppler sonography and a servo-controlled noninvasive device for blood pressure measuring. One group of 8 volunteers (mean age, 27.2+/-3.5 yr; gender, 3 females/5 males) was subjected to cold baths of 22 degrees C for 20 min Another group of 7 volunteers (mean age, 52.1+/-8.5 yr; gender, 4 females/3 males) took hyperthermic baths at rising water temperatures from 36 degrees to 42 degrees C, increased by 1 degree C every 5 min. Each volunteer in both groups underwent autoregulation tests two to four times before, during, and after the thermic bath. Dynamic autoregulation was measured by the response of cerebral blood flow velocity to a transient decrease of the mean arterial blood pressure, induced by rapid deflation of thigh cuffs. The autoregulation index, i.e., a measure of the speed of change of cerebral autoregulation, was used to quantify the response. Further parameters were core temperature, blood pressure (mm Hg) and CO2et. During hypothermic baths, core temperature decreased by 0.3 degrees C (P = 0.001), measured between preliminary phase and the end of the bath; the autoregulation index decreased significantly (P < 0.05) from 5.3 before the bath to 4.25 during the bath. During hyperthermic baths, the autoregulation index increased from 6.0 to 7.5 and 8.9 (P < 0.001), with an increase of core temperature of 0.4 degrees C. The main cerebral autoregulation system is dependent on changes of core temperature, provoked by hypothermic or hyperthermic whole-body thermostimulus. Application of hyperthermic baths increased the autoregulation index, and hypothermic baths decreased the autoregulation index. Further studies are needed to prove the positive effects of thermo-stimulating water applications on cerebral hemodynamics in patients with cerebral diseases.

Ultrasound contrast agents improve the signal-to-noise ratio of reflected ultrasound, enhancing the diagnostic value of transcranial Doppler (TCD). In dog studies, we investigated the time course of TCD signal amplitude after application of a phospholipid-containing ultrasound contrast agent (BY963) filled with different gases. The median time of Doppler amplitude enhancement exceeding 5 dB was determined using isoflurane-, isopentane-, trichlortrifluoroethane-, air-, argon-, and perfluoropentane-filled BY963 (69, 72, 75, 78, 88, and 245 seconds respectively). The decrease of time-intensity curve and the duration of signal enhancement showed significant differences comparing the different gases (p = 0.04 and 0.03, respectively). The time course of in vitro stability of BY963 agitated with the different gases measured by absorbance of light (500 nm) showed a retarded decay for perfluoropentane, a rapid decrease for air, isopentane, trichlortrifluoroethane, and argon, and a very rapid decrease using isoflurane. The time course of the different gases depended on the physiochemical properties (lipophilicity and the solubility in water) of the gas encoated in the phospholipid shell. Perfluoropentane-filled BY963 showed the highest in vitro stability and the longest duration of TCD enhancement compared with the other gases used.

We present the methodology and data indicating the feasibility of a five-study collaborative stroke trial. The core study, the Warfarin-Aspirin Recurrent Stroke Study (WARSS), is a prospective, random

The concept of critical care in stroke is a controversial issue. The question of whether full-scale critical care management of stroke improves patient outcome is still open and probably depends on th

Transcranial color-coded duplex sonography (TCCD) is a new ultrasound technique that adds color-coding of the frequency- or power-based Doppler signal and B-mode imaging to conventional transcranial Doppler sonography (TCD). As conventional TCD this technique identifies stenoses, occlusions and vasospasm of the major basal cerebral arteries. The additions visualize the anatomy and flow direction of the basal cerebral arteries, the ventricular system, parenchymal and bony structures. Thus potentially hazardous compression tests to identify cerebral arteries are rarely necessary, and ultrasonic assessment of cross-flow through the circle of Willis becomes more reliable. Moreover, estimates of insonation angles and measurements of angle-corrected flow velocities become feasible. TCCD may visualize larger (>1 x 1 cm) supratentorial hematomas with subcortical location, and provide incidental diagnosis of cerebral arteriovenous malformations, aneurysms, and hydrocephalus, but is inferior to neuroradiological techniques. The main limitation of TCCD is the acoustic window that may prevent transtemporal insonation in up to 30% of cases. Transpulmonary contrast agents may permit the examination of such patients. Power-based TCCD, used alone or in combination with echo contrast agents or three-dimensional ultrasound imaging, represent important future developments of TCCD.

Background and Purpose We assessed the influence of different visual stimuli and the reproducibility and habituation of evoked flow responses using simultaneous two-channel transcranial Doppler monitoring and flow velocity averaging. Methods We measured stimulus-related percentage changes in posterior cerebral, basilar, and middle cerebral artery blood flow velocities in 14 normal volunteers using stimulus-triggered velocity averaging. With a two-channel transcranial Doppler system, simultaneous measurements in two arteries (both posterior cerebral arteries and the basilar and middle cerebral artery) were taken using multiple-array light-emitting diodes applying flash stimuli. Both posterior cerebral arteries were monitored to assess reproducibility and habituation of the evoked response with repetitive measurements under unchanged conditions and to analyze the influence of different features of the visual stimulus. Results There was a distinctive increase in velocities resulting from visual stimuli in both posterior cerebral and the basilar arteries but not in the middle cerebral artery. The responses in both posterior cerebral arteries were larger than in the basilar artery ( P =.0001). Brightness ( P P Conclusions The use of flow velocity averaging and two-channel simultaneous recording increases the sensitivity of transcranial Doppler monitoring to detect and correlate selective flow changes in the posterior cerebral arteries resulting from cerebral activation produced by visual stimulation.

We compared relative changes in middle cerebral artery velocity and internal carotid artery flow during autoregulation testing to test the validity of using transcranial Doppler recordings of middle cerebral artery velocity to evaluate cerebral autoregulation in humans. Seven human volunteers had dynamic autoregulation tested during surgical procedures that included exposure of the internal carotid artery. The mean arterial blood pressure and middle cerebral artery velocity spectral outline (Vmax), using transcranial Doppler, and ipsilateral internal carotid artery flow, using an electromagnetic flowmeter, were continuously and simultaneously recorded during transient sharp decreases in blood pressure that were induced by rapid deflation of thigh blood pressure cuffs. The resulting responses of velocity in the middle cerebral artery and flow in the internal carotid artery were compared. Moderate decreases in blood pressure evoked responses in cerebral autoregulation. There were no significant (P = .97) differences between the responses in middle cerebral artery velocity and internal carotid artery flow to the blood pressure decreases. Relative changes in Vmax accurately reflect relative changes in internal carotid artery flow during dynamic autoregulation testing in humans. Therefore, alterations in middle cerebral artery diameter do not occur to the extent that they introduce a significant error in making these comparisons.

Eighty-six patients with head injuries with an admission Glasgow Coma Scale score between 3 and 12 were studied sequentially by transcranial and cervical Doppler sonography. On a subset of 26 patients, sequential autoregulation and CO2 reactivity testing was also performed. Patient characteristics and hemodynamic data were correlated and analyzed with respect to the final outcome. The internal carotid artery (ICA) and middle cerebral artery flow velocities followed a typical pattern. Both were depressed during the first 3 days after the trauma and then increased to a maximum between Days 5 and 7. The increase of the middle cerebral artery flow velocities was more pronounced than the increase of the ICA flow velocities, thus indicating some degree of vasospasm. The amount of subarachnoid hemorrhage on the initial computed tomography correlated with the average middle cerebral artery/ICA flow velocity ratio (r = 0.5). Subarachnoid hemorrhages on computed tomography and, to a lesser degree, subdural and intracerebral hematomas were correlated with an unfavorable outcome. Vasospasm remained subcritical, and no negative relationship to outcome could be identified. Hyperperfusion, as based on ICA flow velocities, and vasospasm were correlated with diminished vasoreactivity. However, disturbed vasoreactivities, particularly during the first days, were common and did not necessarily predict an unfavorable outcome.

Knowledge of the velocity with which pressure and flow waves travel within the arterial tree has been fundamental to the understanding of important hemodynamic parameters, such as vessel wall elastance, impedance and reflection coefficients for the systemic circulation. To our knowledge, however, this pulse wave velocity (PWV) has not been previously measured for the human cerebral circulation. In this study, we estimate the PWV from 88 measurements during normocarbia and 95 measurements during hypocarbia in six healthy human volunteers. The measurements consisted of time delays between velocity waveforms obtained simultaneously from the cervical carotid artery and the ipsilateral middle cerebral artery. An estimation of the distance between these sites as 10 centimeters yielded a PWV of 12.8 m/s for both levels of pCO 2 . Vessel elasticity could then be estimated between 17 and 34 dyne/cm 2 · 10 6 . These values of PWV are among the highest of those found in the peripheral circulation, and may have implications for the interpretation of the shape of the cerebral pressure and flow waveforms.

✓ Intracranial pressure (ICP) and continuous transcranial Doppler ultrasound signals were monitored in 20 head-injured patients and simultaneous synchronous fluctuations of middle cerebral artery (MCA) velocity and B waves of the ICP were observed. Continuous simultaneous monitoring of MCA velocity, ICP, arterial blood pressure, and expired CO2 revealed that both velocity waves and B waves occurred despite a constant CO2 concentration in ventilated patients and were usually not accompanied by fluctuations in the arterial blood pressure. Additional recordings from the extracranial carotid artery during the ICP B waves revealed similar synchronous fluctuations in the velocity of this artery, strongly supporting the hypothesis that blood flow fluctuations produce the velocity waves. The ratio between ICP wave amplitude and velocity wave amplitude was highly correlated to the ICP (r = 0.81, p < 0.001). Velocity waves of similar characteristics and frequency, but usually of shorter duration, were observed in seven of 10 normal subjects in whom MCA velocity was recorded for 1 hour. The findings in this report strongly suggest that B waves in the ICP are a secondary effect of vasomotor waves, producing cerebral blood flow fluctuations that become amplified in the ICP tracing, in states of reduced intracranial compliance.

The aim of the present study was to evaluate the time course for cerebral autoregulation (AR) recovery following severe traumatic brain injury (TBI).Thirty-six patients (27 males and 9 females, mean +/- SEM age 33 +/- 15.1 years) with severe TBI underwent serial dynamic AR studies with leg cuff deflation as a stimulus, until recovery of the AR responses was measured.The AR was impaired (AR index2.8) in 30 (83%) of 36 patients on Days 3-5 after injury, and in 19 individuals (53%) impairments were found on Days 9-11 after the injury. Nine (25%) of 36 patients exhibited a poor AR response (AR index1) on postinjury Days 12-14, which eventually recovered on Days 15-23. Fifty-eight percent of the patients with a Glasgow Coma Scale score of 3-5, 50% of those with diffuse brain injury, 54% of those with elevated intracranial pressure, and 40% of those with poor outcome had no AR recovery in the first 11 days after injury.Autoregulation recovery after severe TBI can be delayed, and failure to recover during the 2nd week after injury occurs mainly in patients with a lower Glasgow Coma Scale score, diffuse brain injury, elevated ICP, or unfavorable outcome. The finding suggests that perfusion pressure management should be considered in some of the patients for a period of at least 2 weeks.

Ischemic stroke is a common and disabling complication of sickle cell disease (Hb SS). Most infarctions occur in the presence of intracranial stenotic lesions of the large vessels of the circle of Willis. Transcranial Doppler (TCD), by measuring flow velocity in these arterial segments, can detect focal stenosis on the basis of elevated flow velocity. We report the preliminary results of a prospective study to develop criteria for detection of stenotic lesions based on TCD and identification of patients with Hb SS at risk for stroke. Comparing the TCD findings from six patients with lesions demonstrated by angiography to those from 115 Hb SS children without stroke, we conclude: (a) middle cerebral (MCA), anterior cerebral (ACA), or internal carotid (ICA) artery mean velocities greater than 190 cm/s strongly suggest focal stenosis; (b) MCA or ACA mean velocities of 150 to 190 cm/s suggest abnormality but at present cannot be considered diagnostic of stenosis; (c) mean velocities up to 150 cm/s are possibly due to the effects of low hematocrit and/or young age, and cannot as yet be distinguished from velocity elevations due to vessel stenosis.

Background and Purpose— Dynamic cerebral autoregulation has been shown to be fast and effective, but it is not well known if the mechanism is symmetric, that is to say, it acts with equal compensatory action to upward as compared with downward abrupt changes in arterial blood pressure (ABP). Methods— Fourteen patients with head injuries and 10 normal subjects had bilateral transcranial Doppler and continuous ABP recording. Cyclic ABP stimuli were generated by large thigh cuffs, which were rapidly inflated above systolic pressure for 15 seconds alternating with 15 seconds of deflation. At least 8 such cycles were ensemble-averaged and the dynamic autoregulatory gain (AG up and AG dn ) was estimated separately for upward and downward changes in ABP. The results were compared with the autoregulation index using conventional leg cuff releases. Results— In normal subjects, AG dn was 0.74±0.18 and AG up was 0.77±0.17 (mean±SD); the difference was insignificant. The correlation between AG dn and AG up , however, was weak ( r =0.24). In the patients with head injury, AG dn was 0.30±0.21 and AG up was 1.27±0.76, the difference being highly significant ( P dn and AG up ( r =−0.33). Autoregulation index correlated well with AG dn ( r =0.79) and weakly negatively with AG up ( r =−0.47). Conclusions— A strongly asymmetric dynamic response of the cerebral autoregulation was seen the majority of patients with head injury. It might also have been present, albeit to a lesser degree, in the normal subjects. The findings suggest that nonlinear effects may be present in the operation of the cerebral autoregulation mechanism.

Various aspects of the cerebral blood-flow regulation can be assessed by transcranial Doppler (TCD). This chapter describes and discusses the approaches that have been reported in the literature. The steady-state characteristics of the cerebral autoregulation can be determined by changing the blood pressure level, and calculating the response of the vasomotors. Moreover, the lower limit of the autoregulatory 'plateau' can be investigated after lowering the blood pressure by pharmacological means. The excellent time-resolution of the TCD technique also facilitates the determination of the quasi-stationary and dynamic aspects of the autoregulatory response. The leg-cuff method shows that regulatory action is very fast, compensating for a sharp drop in blood pressure within seconds. Less intrusively, the autoregulatory characteristics can be assessed from recordings of spontaneous variations in blood pressure. Transfer function methods describe the faster aspects of the mechanism, while correlation techniques reveal the quasi-stationary characteristics. However, the repeatability and accuracy of methods based on spontaneous fluctuations are probably less than those of stimulus-response tests. In this chapter, the various CO2 and acetazolamide approaches that determine vasomotor reactivity are described and discussed.

Various aspects of the cerebral blood-flow regulation can be assessed by transcranial Doppler (TCD). This chapter describes and discusses the approaches that have been reported in the literature. The steady-state characteristics of the cerebral autoregulation can be determined by changing the blood pressure level, and calculating the response of the vasomotors. Moreover, the lower limit of the autoregulatory 'plateau' can be investigated after lowering the blood pressure by pharmacological means. The excellent time-resolution of the TCD technique also facilitates the determination of the quasi-stationary and dynamic aspects of the autoregulatory response. The leg-cuff method shows that regulatory action is very fast, compensating for a sharp drop in blood pressure within seconds. Less intrusively, the autoregulatory characteristics can be assessed from recordings of spontaneous variations in blood pressure. Transfer function methods describe the faster aspects of the mechanism, while correlation techniques reveal the quasi-stationary characteristics. However, the repeatability and accuracy of methods based on spontaneous fluctuations are probably less than those of stimulus-response tests. In this chapter, the various CO2 and acetazolamide approaches that determine vasomotor reactivity are described and discussed.

Background and Purpose— Transcranial Doppler has been extensively used to measure cerebrovascular control mechanisms, including autoregulation in humans and in patients with cerebrovascular diseases. There have been sufficient reports on the measurement of normal autoregulatory response (AR) and CO 2 reactivity (CR) of the middle cerebral artery (MCA) but few reports of these indices for the basilar artery (BA). We measured AR and CR in the BA in healthy volunteers to determine normal values and compared them with simultaneous measurements made in the MCA. Methods— Sixteen normal subjects were enrolled. Time-averaged mean velocities of maximum blood flow in the BA and MCA were continuously and simultaneously monitored by using transcranial Doppler along with continuous measurement of mean arterial blood pressure (MABP). Values were obtained during rest, alterations of end-tidal Pa co 2 (ETCO 2 ), and acute decrease and recovery of MABP. AR was evaluated by using the thigh cuff method and graded by the standard dynamic autoregulatory index (ARI), with values between 0 and 9. CR was measured as percentage change in time-averaged mean velocity per mm Hg ETCO 2 . Results— The mean age of 16 subjects was 27.38±8.50 years. Average baseline values for MABP and ETCO 2 were 82.29±7.10 and 42.75±3.77 mm Hg, respectively. Mean ARI was 4.62±1.26 for the BA and was 4.77±1.23 for the MCA (n=15) ( P =0.598). Average CR was 2.54±0.39%/mm Hg ETCO 2 for the BA and 2.51±0.29%/mm Hg ETCO 2 for the MCA (n=16) ( P =0.686). Conclusions— Our study demonstrates that ARI and CR values for the BA are similar to those for the MCA.

An understanding of the hemodynamics of cerebrovascular spasm following subarachnoid hemorrhage is important for the diagnosis and treatment of this potentially dangerous condition. An overview model is presented which includes the main elements determining the overall effect of vasospasm. The model included realistic pressureflow-velocity-diameter relationships encountered in a geometry resembling that of vasospasm of the middle cerebral artery. Viscosity was adjusted to that expected of human blood. Furthermore, a realistic model the cerebral autoregulation was included. The effects of induced hypertension as well as hypotension were studied.

Transcranial Doppler (TCD) can monitor middle cerebral artery (MCA) velocity which can be recorded simultaneously with other physiologic parameters such as end tidal (Et) CO2, arterial blood pressure and intracranial pressure (ICP), in head injured patients. Relative changes in MCA velocity can be used to reflect relative MCA blood flow changes during ICP waves, and also to evaluate cerebral autoregulation, CO2 reactivity and hemodynamic responses to mannitol and barbiturates. The utility and practicality of short intervals of TCD monitoring to evaluate hemodynamic responses, was evaluated in a group of 22 head injured patients (average Glasgow coma score 6). During ICP A waves, MCA velocity always decreased during the peak of the wave, and during ICP B waves, fluctuated synchronously with the ICP. Dynamic cerebral autoregulation, and reactivity to CO2, were reduced within 48 hours of admission. Impaired cerebral autoregulation within 48 hours of admission did not correlate with outcome at 1 month. Mannitol infusion caused an increase in MCA velocity (15.4 +/- 7.9%) which was significantly correlated to the impairment of dynamic autoregulation (r = 0.54, p0.0001). The MCA velocity response to a test dose of barbiturates was significantly correlated to the ICP (r = 0.61, p0.01) response as well as to the CO2 reactivity (r = 0.37, p0.05). Continuous MCA velocity monitoring using TCD may be useful in evaluating a variety of hemodynamic responses in head injury patients and may replace more cumbersome cerebral blood flow techniques which have been used in the past for these purposes.

OBJECTIVE : This study was undertaken to evaluate the effect of acute moderate hyperventilation on cerebral autoregulation in head-injured patients. METHODS : Dynamic cerebral autoregulation was analyzed by use of transcranial doppler ultrasonography before and after hyperventilation in 10 patients with severe head injury. All of the patients were artificially ventilated and underwent continuous monitoring of arterial blood pressure, intracranial pressure, and end-tidal carbon dioxide. To test autoregulation, rapid transient decreases in systemic blood pressure were achieved by quickly releasing large blood pressure cuffs that were inflated around both thighs. This resulted in a drop of 24 ± 6 mm Hg in mean systemic blood pressure, which lasted an average of 49 ± 24 seconds. Cerebral blood flow velocity was monitored continuously in both middle cerebral arteries by use of transcranial doppler ultrasonography. The percentage change in middle cerebral artery velocity was used as an index of the change in cerebral blood flow during the autoregulatory response. The change in estimated cerebrovascular resistance, immediately after the blood pressure drop, or the rate of regulation was used to analyze the effectiveness of the cerebral autoregulation. This value was calculated by determining the rate of increase in middle cerebral artery velocity during the 1st 5 seconds after a blood pressure drop, relative to the rate of increase of the cerebral perfusion pressure. RESULTS : The average rate of regulation during normocapnia at pCO 2 of 37 mm Hg was 11.4 ± 5% per second. After reduction of the pCO 2 to 28 mm Hg, the average rate of regulation improved significantly (P < 0.001 ) to 17.7 ± 6% per second. Autoregulation improved, despite no significant change in the cerebral perfusion pressure during hyperventilation. The degree of improvement in autoregulation was significantly correlated with the CO 2 reactivity (r = 0.45, P < 0.05) but did not correlate (r = -0.23, P = 0.33) with the change in arterial pH value after hyperventilation. CONCLUSION : These results confirm the finding that dynamic autoregulation is disturbed in severe head injury and that moderate transient hyperventilation can temporarily improve the efficiency of the autoregulatory response, probably as a result of a transient increase in vascular tone.

Background and Purpose Cerebral autoregulation can be evaluated by measuring relative blood flow changes in response to a steady-state change in the blood pressure (static method) or during the response to a rapid change in blood pressure (dynamic method). The purpose of this study was to compare the results of the two methods in humans with both intact and impaired autoregulatory capacity. Methods Using intraoperative transcranial Doppler sonography recordings from both middle cerebral arteries, we determined static and dynamic autoregulatory responses in 10 normal subjects undergoing elective surgical procedures. The changes in cerebrovascular resistance were estimated from the changes in cerebral blood flow velocity and arterial blood pressure in response to manipulations of blood pressure. Static autoregulation was determined by analyzing the response to a phenylephrine-induced rise in blood pressure, whereas rapid deflation of a blood pressure cuff around one thigh served as a stimulus for testing dynamic autoregulation. Both measurements were performed in patients with intact autoregulation during propofol anesthesia and again in the same patients after autoregulation had been impaired by administration of high-dose isoflurane. Results There was a significant reduction in autoregulatory capacity after the administration of high-dose isoflurane, which could be demonstrated using static ( P P r =.93, P Conclusions These data show that in normal human subjects measurement of dynamic autoregulation yields similar results as static testing of intact and pharmacologically impaired autoregulation.

Transcranial color-coded duplex sonography (TCCD), magnetic resonance angiography (MRA), and computed tomography angiography (CTA) are novel noninvasive or minimally invasive techniques for the study of the intracranial circulation. TCCD is relatively inexpensive and permits bedside examination. It improves the accuracy and reliability of conventional transcranial Doppler studies. The main limitation of TCCD are the ultrasonic windows. They restrict the area of insonation to the major cerebral arteries and the proximal part of its branches, lower the spatial resolution, and may prevent transtemporal insonation. Using MRA, both large and small intracranial arteries and veins can be imaged by selecting the appropriate imaging parameters. MRA provides morphologic information about the cerebral vessels, relying on blood flow as the physical basis for generating contrast between stationary tissues and moving spins. MRA is highly sensitive for the detection of occlusive disease in large intracranial arteries. However, with bright blood techniques the degree of stenosis tends to be exaggerated. Flow direction, eg, in collaterals, can be determined by selective or phase-contrast MRA. Perfusion imaging techniques provide information about blood flow at the capillary level. Diffusion imaging depicts molecular motion. TCCD and MRA used in combination or alone may eliminate the need for intra-arterial digital subtraction angiography (DSA) in most patients studied for occlusive cerebrovascular disease. DSA may be reserved for those patients where there is disagreement among the noninvasive techniques, and for the diagnosis of cerebral aneurysms and arteriovenous malformations. CTA relies on spiral CT technology and intravenous contrast injection. To date, intracranial use has been predominantly for the diagnosis of aneurysms. The role of CTA for the detection of nonaneurysmal intracranial vascular disease has yet to be established.

The exact mechanism responsible for B waves is unclear, however it has been attributed to cerebral blood flow (CBF) fluctuations, thought to be secondary to respiratory variations during abnormal breathing patterns in neurosurgical patients [6]. Transcranial Doppler (TCD) monitoring of blood flow velocity has demonstrated velocity fluctuations at frequencies similar to those of B waves in head injured patients and also in normal subjects [5, 8, 9], Recording of TCD and intracranial pressure (ICP) signals simultaneously has demonstrated synchronous variations in both parameters [5].

Continuous recording of basal cerebral artery velocities using transcranial Doppler may provide a more practical alternative to CBF methods for the assessment of cerebrovascular responses in patients with head injury and other neurological conditions requiring ICP management. A method is described where continuous recordings of blood flow velocity (BFV), arterial blood pressure (ABP), intracranial pressure (ICP), and end tidal CO2 (Et CO2) are obtained by portable equipment which can easily be taken to the ICU. This unit can then be used to test blood flow response to CO2 changes, autoregulation, response to barbiturates and response to mannitol therapy. By obtaining information on the effectiveness of these responses in head injury patients, it may be feasible to use this information to guide therapy.

Background and Purpose We assessed the influence of different visual stimuli and the reproducibility and habituation of evoked flow responses using simultaneous two-channel transcranial Doppler monitoring and flow velocity averaging. Methods We measured stimulus-related percentage changes in posterior cerebral, basilar, and middle cerebral artery blood flow velocities in 14 normal volunteers using stimulus-triggered velocity averaging. With a two-channel transcranial Doppler system, simultaneous measurements in two arteries (both posterior cerebral arteries and the basilar and middle cerebral artery) were taken using multiple-array light-emitting diodes applying flash stimuli. Both posterior cerebral arteries were monitored to assess reproducibility and habituation of the evoked response with repetitive measurements under unchanged conditions and to analyze the influence of different features of the visual stimulus. Results There was a distinctive increase in velocities resulting from visual stimuli in bo...

✓ The purpose of this study was to determine whether patients with minor head injury experience impairments in cerebral autoregulation. Twenty-nine patients with minor head injuries defined by Glasgow Coma Scale (GCS) scores of 13 to 15 underwent testing of dynamic cerebral autoregulation within 48 hours of their injury using continuous transcranial Doppler velocity recordings and blood pressure recordings. Twenty-nine age-matched normal volunteers underwent autoregulation testing in the same manner to establish comparison values. The function of the autoregulatory response was assessed by the cerebral blood flow velocity response to induced rapid brief changes in arterial blood pressure and measured as the autoregulation index (ARI). Eight (28%) of the 29 patients with minor head injury demonstrated poorly functioning or absent cerebral autoregulation versus none of the controls, and this difference was highly significant (p = 0.008). A significant correlation between lower blood pressure and worse autoregulation was found by regression analysis in head-injured patients (r = 0.6, p < 0.001); however, lower blood pressure did not account for the autoregulatory impairment in all patients. Within this group of head-injured patients there was no correlation between ARI and initial GCS or 1-month Glasgow Outcome Scale scores. This study indicates that a significant number of patients with minor head injury may have impaired cerebral autoregulation and may be at increased risk for secondary ischemic neuronal damage.

Background Although inhalation anesthetic agents are thought to impair cerebral autoregulation more than intravenous agents, there are few controlled studies in humans. Methods In the first group (n = 24), dynamic autoregulation was assessed from the response of middle cerebral artery blood flow velocity (Vmca) to a transient step decrease in mean arterial blood pressure (MABP). The transient hypotension was induced by rapid deflation of thigh cuffs after inflation for 3 min. In the second group (n = 18), static autoregulation was studied by observing Vmca in response to a phenylephrine-induced increase in MABP. All patients were studied during fentanyl (3 micrograms.kg-1.h-1)/nitrous oxide (70%) anesthesia, followed by, in a randomized manner, isoflurane, desflurane, or propofol in a low dose (0.5 MAC or 100 micrograms.kg-1.min-1) and a high dose (1.5 MAC or 200 micrograms.kg-1.min-1). The dynamic rate of regulation (dROR) was assessed from the rate of change in cerebrovascular resistance (MABP/Vmca) with the blood pressure decreases using computer modeling, whereas the static rate of regulation (sROR) was assessed from the change in Vmca with the change in MABP. Results Low-dose isoflurane delayed (dROR decreased) but did not reduce the autoregulatory response (sROR intact). Low-dose desflurane decreased both dROR and sROR. During 1.5 MAC isoflurane or desflurane, autoregulation was ablated (both dROR and sROR impaired). Neither dROR nor sROR changed with low- or high-dose propofol. Conclusions At 1.5 MAC, isoflurane and desflurane impaired autoregulation whereas propofol (200 micrograms.kg-1.min-1) preserved it.

✓ A transcranial ultrasonic method for the recording of murmurs from cerebral vessels is described. Using the new approach the authors have observed musical murmurs of pure tone quality in 15 patients with increased flow velocities in the cerebral arteries after spontaneous subarachnoid hemorrhage (SAH). The frequency range of the pure tones was from 140 to 820 Hz, corresponding to flow velocities between 73 and 215 cm/sec. The musical murmurs occurred as a transitional state between silent flow and the well known phenomenon of bruit. They were observed between the 4th and the 20th day after SAH. The most likely cause of the musical murmur is a periodic shedding of vortices in the cerebral arteries, commonly referred to as “a von Kármán vortex street.” Clinically the presence of musical murmurs indicated that pathologically increased blood velocities were present in the artery under investigation. This probably reflected the degree of spasm.

An unconventional analog-to-digital converter and multiplexer is described. The instrument is based on conversion of the analog signals to time intervals between narrow-width pulses by an encoder unit. The coded analog signals may then be transferred on a single line to a decoder unit and/or stored on a single track of an AM magnetic tape recorder for later processing. The signals are digitized in the decoder unit by measuring the time intervals between the pulses by means of a binary counter driven by a 19.8-MHz oscillator. The decoder is directly communicating with the interface of a digital computer, and a software package has been written for the control of data transmission. The performance of the instrument in our version is: eight separate analog inputs, sampling rate 200 Hz, input voltage −1.6 to 1.6 V, resolution capacity 3.2 V/213, noise ≈0.1%, signal bandwidth de to 50 Hz ac.

✓ The use of an ultrasonic transcranial Doppler technique for noninvasive evalution of cerebral vasospasm is described. Middle cerebral arteries (MCA's), classified as spastic on angiography, demonstrated blood-flow velocity between 120 and 230 cm/sec. The flow velocities in these arteries had a clear inverse relationship to the diameter as measured from angiograms in 38 patients with recent subarachnoid hemorrhage. This relationship in the proximal anterior cerebral artery (ACA) was found to be more complicated to assess, due to the collateral channels in the anterior part of the circle of Willis. The authors conclude, however, that the new method of measuring vasospasm will also detect spasm in the ACA if it has a hemodynamically significant effect upon flow resistance.

We studied the response of cerebral blood flow to acute step decreases in arterial blood pressure noninvasively and nonpharmacologically in 10 normal volunteers during normocapnia, hypocapnia, and hypercapnia. The step (approximately 20 mm Hg) was induced by rapidly deflating thigh blood pressure cuffs following a 2-minute inflation above systolic blood pressure. Instantaneous arterial blood pressure was measured by a new servo-cuff method, and cerebral blood flow changes were assessed by transcranial Doppler recording of middle cerebral artery blood flow velocity. In hypocapnia, full restoration of blood flow to the pretest level was seen as early as 4.1 seconds after the step decrease in blood pressure, while the response was slower in normocapnia and hypercapnia. The time course of cerebrovascular resistance was calculated from blood pressure and blood flow recordings, and rate of regulation was determined as the normalized change in cerebrovascular resistance per second during 2.5 seconds just after the step decrease in blood pressure. The reference for normalization was the calculated change in cerebrovascular resistance that would have nullified the effects of the step decrease in arterial blood pressure on cerebral blood flow. The rate of regulation was 0.38, 0.20, and 0.11/sec in hypocapnia, normocapnia, and hypercapnia, respectively. There was a highly significant inverse relation between rate of regulation and PaCO2 (p less than 0.001), indicating that the response rate of cerebral autoregulation in awake normal humans is profoundly dependent on vascular tone.

The strength of aneurysm walls obtained intraoperatively or at autopsy immediately after death was evaluated by measurements of the force response to one-directional stretch and compared to the walls of intracranial arteries. The maximum stress that aneurysm tissue could tolerate was found slightly lower than in arteries, which is most probably due to the amount of immature forms of collagen. The stress resistance of aneurysms and arterial tissue decayed over a period of several hours. The relaxation curve could be approximated by the sum of 2 exponential terms. The half decay times of these terms were found identical in aneurysms and arteries, they appear to be collagen characteristics. The strength measured in vitro was compared to the stress in vivo, which was calculated on the basis of blood pressure and aneurysm radius. The stress tolerated by aneurysm walls over a period of 24 hours was found to be in the range of the stress that is imposed in vivo by the mean blood pressure. Arteries resisted stresses corresponding to pressures 10 to 20 times higher than physiological values. The thickness of the aneurysm walls correlated with the aneurysm radius in a linear fashion. It is suggested that aneurysm growth can be understood as passive yield to blood pressure, and reactive healing and thickening of the wall with increasing aneurysm diameter.

✓Blood flow velocities in basal cerebral arteries were recorded noninvasively in 28 patients with cerebral arteriovenous malformations (AVM's) and were correlated with the angiographic findings. In normal arteries remote from the AVM, flow velocities ranged from 44 to 94 cm/sec (median 65 cm/sec) with pulsatility indexes from 0.65 to 1.10 (median 0.87). This is consistent with findings in normal individuals. Arteries feeding the AVM's were identified by the high flow velocities (ranging from 75 to 237 cm/sec, median 124 cm/sec). The pulsatility index ranged from 0.22 to 0.74 (median 0.48). The difference of these results from findings in normal remote arteries was highly significant (p < 0.001). Hyperventilation tests illustrated the hemodynamic difference between an AVM and normal cerebrovascular beds. Flow velocity measurements permitted noninvasive diagnosis of AVM's in 26 of the 28 patients. Furthermore, the identification of individual feeding arteries permitted good definition of the anatomical localization of individual AVM's. Flow velocity measurements combined with computerized tomography scans are useful in the diagnosis of AVM's. With the feeding artery's configuration identified on angiography, flow velocity measurements permit a new insight into the “hemodynamic dimension” of an AVM and its possible effects on adjacent normal brain-tissue perfusion in the individual patient.

Observations on blood velocity in the middle cerebral artery using transcranial Doppler ultrasound and on the ipsilateral internal carotid artery flow volume were obtained during periods of transient, rapid blood flow variations in 7 patients. Five patients were investigated after carotid endarterectomy. A further 2 patients having staged carotid endarterectomy and open heart surgery were investigated during nonpulsatile cardiopulmonary bypass. The patient selection permitted the assumption that middle cerebral artery flow remained proportional to internal carotid artery flow. The integrated time-mean values from consecutive 5-second periods were computed. The arithmetic mean internal carotid artery flow varied from 167 to 399 ml/min in individual patients, with individual ranges between +/- 15% and +/- 35% of the mean flow. The mean middle cerebral artery blood velocity varied from 32 to 78 cm/sec. The relation between flow volume and blood velocity was nearly linear under these conditions. Normalization of the data as percent of the individual arithmetic means permitted a composite analysis of data from all patients. Linear regression of normalized blood velocity (V') on normalized flow volume (Q') showed V' = 1.05 Q' - 5.08 (r2 = 0.898).