Adaptive feedback analysis and control of programmable stimuli for assessment of cerebrovascular function

The assessment of cerebrovascular regulatory mechanisms often requires flexibly controlled and precisely timed changes in arterial blood pressure (ABP) and/or inspired CO2. In this study, a new system for inducing variations in mean ABP was designed, implemented and tested using programmable sequences and programmable controls to induce pressure changes through bilateral thigh cuffs. The system is also integrated with a computer-controlled switch to select air or a CO2/air mixture to be provided via a face mask. Adaptive feedback control of a pressure generator was required to meet stringent specifications for fast changes, and accuracy in timing and pressure levels applied by the thigh cuffs. The implemented system consists of a PC-based signal analysis/control unit, a pressure control unit and a CO2/air control unit. Initial evaluations were carried out to compare the cuff pressure control performances between adaptive and non-adaptive control configurations. Results show that the adaptive control method can reduce the mean error in sustaining target pressure by 99.57 % and reduce the transient time in pressure increases by 45.21 %. The system has proven a highly effective tool in ongoing research on brain blood flow control

Detection of impaired cerebral autoregulation improves by increasing arterial blood pressure variability

Although the assessment of dynamic cerebral autoregulation (CA) based on measurements of spontaneous fluctuations in arterial blood pressure (ABP) and cerebral blood flow (CBF) is a convenient and much used method, there remains uncertainty about its reliability. We tested the effects of increasing ABP variability, provoked by a modification of the thigh cuff method, on the ability of the autoregulation index to discriminate between normal and impaired CA, using hypercapnia as a surrogate for dynamic CA impairment. In 30 healthy volunteers, ABP (Finapres) and CBF velocity (CBFV, transcranial Doppler) were recorded at rest and during 5% CO(2) breathing, with and without pseudo-random sequence inflation and deflation of bilateral thigh cuffs. The application of thigh cuffs increased ABP and CBFV variabilities and was not associated with a distortion of the CBFV step response estimates for both normocapnic and hypercapnic conditions (P=0.59 and P=0.96, respectively). Sensitivity and specificity of CA impairment detection were improved with the thigh cuff method, with the area under the receiver-operator curve increasing from 0.746 to 0.859 (P=0.031). We conclude that the new method is a safe, efficient, and appealing alternative to currently existing assessment methods for the investigation of the status of CA

Revisiting the frequency domain: the multiple and partial coherence of cerebral blood flow velocity in the assessment of dynamic cerebral autoregulation

Despite advances in modelling dynamic autoregulation, only part of the variability of cerebral blood flow velocity (CBFV) in the low frequency range has been explained. We investigate whether a multivariate representation can be used for this purpose. Pseudorandom sequences were used to inflate thigh cuffs and to administer 5% CO2. Multiple and partial coherence were estimated, using arterial blood pressure (ABP), end-tidal CO2 (EtCO2) and resistance area product as input and CBFV as output variables. The inclusion of second and third input variables increased the amount of CBFV variability that can be accounted for (p  <  10−4 in both cases). Partial coherence estimates in the low frequency range (<0.07 Hz) were not influenced by the use of thigh cuffs, but CO2 administration had a statistically significant effect (p  <  10−4 in all cases). We conclude that the inclusion of additional inputs of a priori known physiological significance can help account for a greater amount of CBFV variability and may represent a viable alternative to more conventional non-linear modelling. The results of partial coherence analysis suggest that dynamic autoregulation and CO2 reactivity are likely to be the result of different physiological mechanisms

Coherent averaging of pseudorandom binary stimuli: is the dynamic cerebral autoregulatory response symmetrical?

Objective: Previous studies on cerebral autoregulation have shown the existence of hemispheric symmetry, which may be altered in stroke and traumatic brain injury. There is a paucity of data however on whether the response is symmetrical between those disturbances that cause cerebral hyperperfusion, to those that cause hypoperfusion. Our aim was to investigate whether the responses of cerebral autoregulation to haemodynamic stimuli of different directions are symmetrical. &#13; Approach: Using a previously described assessment method, we employed coherent averaging of the cerebral blood flow velocity (CBFV) responses to thigh cuff inflation and deflation, as driven by pseudorandom binary sequences, whilst simultaneously altering the inspired CO2. The symmetry of the autoregulatory response was assessed with regards to two parameters, its speed and gain. Using the first harmonic method, critical closing pressure (CrCP) and resistance area product (RAP) were estimated, and the gain of the autoregulatory response was calculated by performing linear regression between the coherent averages of arterial blood pressure (ABP) and CBFV, ABP and CrCP and finally ABP and RAP. A two-way repeated measures ANOVA was used to assess for the effect of the direction of change in ABP and the method of CO2 administration. &#13; Main results: Our results suggest that whilst the direction of ABP change does not have a significant effect, the effect of CO2 administration method is highly significant (p&lt;10-4). &#13; Significance: This is the first report to report to demonstrate the symmetry of the autoregulatory response to stimuli of different directions as well as the short term dynamics of RAP and CrCP under intermittent and constant hypercapnia. As haemodynamic stimulus direction does not appear to have an influence, our findings validate previous work done using different assessment methods

Spectral and time-frequency analysis of ultrasonic Doppler signals.

Spectral analysis of Doppler signals plays a very important role in non-invasive measurements of blood velocity distributions. Among the various spectral analysis methods available, the fast Fourier transform (FFT) is regarded as a "traditional" spectral analysis tool and is widely used in commercial, clinical, experimental and research equipment. Some drawbacks of this method, however, have imposed limitations on its use in some clinical cases. A numbers of spectral and time-frequency analysis methods have been studied in this dissertation. These include the traditional FFT, the autoregressive (AR) method, the Wigner-Ville distribution (WVD), and the Choi-Williams distribution (CWD). The advantages and disadvantages of each method have been studied and summarised. Efforts have been made to improve the temporal and frequency resolution of the results. New analysis methods such as the WVD and CWD have been interpreted physically, and some of their new properties have been explored. The results have suggested that the heights of the peaks in the AR spectra of narrow-band signals are not necessarily proportional to signal power, and should be used with caution in the context of Doppler signal processing. The results have also shown that it is appropriate to use the WVD or CWD to analyse signals when high temporal resolution is required. In practice, it is easier for the operator to handle the WVD, which usually produces reasonably good results. The above methods have been applied in practice. Considerable software and hardware development has been carried out, and a number of analysers have been implemented for use under different practical conditions. These analysers were also used to compare experimentally the analysis methods mentioned above, and to confirm the results of theoretical analyses. Some of these analysers have found applications in clinical practice

Enhanced Detection of Thromboemboli With the Use of Targeted Microbubbles

Background and Purpose: Targeted ultrasound contrast agents have recently been developed to adhere selectively to specific pathogenic materials such as plaque or thrombus. Administration of such microbubbles has potential to aid transcranial Doppler ultrasound (TCD) detection of emboli, and to act as markers for distinguishing one embolic material from another. The purpose of this study was to investigate whether TCD detection of circulating thrombus emboli would be enhanced by the addition of targeted microbubbles. Methods: Binding of microbubbles to the surface of the thrombus was confirmed using Scanning Electron Microscopy. Targeted and control bubbles were then introduced to thrombus and tissue-mimicking material circulated under pulsatile flow conditions in an in vitro flow-rig. Embolic signal intensities before and after introduction of the bubbles were measured using transcranial Doppler ultrasound. Results: Targeted microbubbles enhanced Doppler signal intensities from thrombus emboli by up to 13 dB. The bubbles were capable of binding to moving thrombus when injected into the flow-circuit in low concentrations (~ 30 bubbles per 100 ml), and were retained on the thrombus under pulsatile-flow conditions. Signal intensities from similarly sized pieces of tissue mimicking material were not enhanced by injection of targeted bubbles. Conclusions: Injection of appropriately targeted microbubbles significantly enhances ultrasound detection of circulating thrombus emboli in vitro, and has potential to assist clinicians in distinguishing thrombus emboli from atheromatous plaque

Random perturbations of arterial blood pressure for the assessment of dynamic cerebral autoregulation

The assessment of cerebral autoregulation (CA) relies mostly on methods that modulate arterial blood pressure (ABP). Despite advances, the gold standard of assessment remains elusive and clinical practicality is limited. We investigate a novel approach of assessing CA, consisting of the intermittent application of thigh cuffs using square wave sequences. Our aim was to increase ABP variability whilst minimizing volunteer discomfort, thus improving assessment acceptability. Two random square wave sequences and two maximum pressure settings (80 and 150 mmHg) were used, corresponding to four manoeuvres that were conducted in random order after a baseline recording. The intermittent application of thigh cuffs resulted in an amplitude dependent increase in ABP (p = 0.001) and cerebral blood flow velocity (CBFV) variability (p = 0.026) compared to baseline. No statistically significant differences in mean heart rate or heart rate variability were observed (p = 0.108 and p = 0.350, respectively), suggesting that no significant sympathetic response was elicited. No significant differences in the CBFV step response were observed, suggesting no distortion of autoregulatory parameters resulted from the use of thigh cuffs. We conclude that pseudorandom binary sequences are an effective and safe alternative for increasing ABP variability. This new approach shows great promise as a tool for the robust assessment of CA.<br/