The technique of transcranial Doppler ultrasound (TCD) was used to assess cerebral blood flow (CBF) in humans. Studies were performed at rest and during dynamic submaximal exercise. In the resting experiments, TCD was combined with the technique of dynamic end-tidal forcing to study the dynamics of the CBF response to step changes in end-tidal (i.e. arterial) PC02 and PO2 In the resting and exercise experiments, the degree of consistency was examined between three indices of CBF that can be extracted from the TCD spectrum. Finally, the ventilatory and the CBF responses to acute isocapnic hypoxia were examined to try to quantify the possible reduction in ventilation that could be attributed to changes in CBF with hypoxia. In the studies performed at rest, during either hypoxia and/or hypercapnia (Chapter 2), the three indices of CBF extracted from the TCD spectrum were all consistent. However, during submaximal exercise (Chapter 5), the indices were less consistent and results suggest that the increase in CBF with exercise that has been reported with TCD needs to be treated with caution. The dynamic studies of the CBF response to step changes in end-tidal PC02 and PO2 in humans revealed that the CBF response to hypercapnia (Chapter 3) is characterised by a significant asymmetry, with a slower on-transient than off-transient, and also by a degree of undershoot following the relief of hypercapnia. The CBF response to hypocapnia (Chapter 4) is also characterised by a significant asymmetry, with a faster on-transient than off-transient. Furthermore, there is a slow progressive adaptation throughout the hypocapnic period. These studies show that the CBF responses to hypercapnia and hypocapnia are much faster than previously been thought. Finally, the work described in Chapter 6 attempts to quantify the possible reduction in ventilation that could be attributed to changes in CBF with hypoxia to determine whether it could be of sufficient magnitude to underlie hypoxic ventilatory decline (HVD). The results suggest that, in awake humans, changes in CBF during acute isocapnic hypoxia are quantitatively insufficient to underlie HVD.

The use of transcranial Doppler (TCD) ultrasound for the assessment of cerebral blood flow velocity (CBFV) provides an indication of cerebral blood flow assuming the diameter of the insonated vessel remains constant. Studies using TCD have traditionally described cerebrovascular hemodynamics with respect to CBFV and cerebrovascular resistance (CVRi); however, a more complete assessment of the cerebral circulation can be gleaned from the analysis of within beat characteristic of the TCD velocity waveform for the determination of cerebrovascular tone. Therefore, the general purpose of the presented studies was to assess CBFV responses and within beat characteristic for the description of cerebrovascular hemodynamics after long duration spaceflight, with sustained orthostasis, in response to changes in the partial pressure of end tidal carbon dioxide (PETCO2), and with NG stimulation. After long duration spaceflight, cerebrovascular autoregulation was found to be impaired along with a reduction in cerebrovascular CO2 reactivity (Study 1). Additionally, critical closing pressure (CrCP) was found to be increased suggesting potential remodelling of the cerebrovasculature contributing to an increase in cerebrovascular tone (Study 2). With sustained orthostasis, CBFV was found to progressively decrease and to be related to reductions in PETCO2 and increases in CrCP suggesting the contribution of changes in cerebrovascular tone leading to the development of syncope (Study 4). The CBFV reduction with the progression towards syncope was also associated with changes in waveform morphology such that the dicrotic notch point was less than the end diastolic value (Study 3). Mathematical modelling (RCKL) was used to further assess changes in cerebrovascular hemodynamics for physiological interpretation of changes in CBFV waveform morphology and found that the amplitude of the dicrotic notch and the calculation of the augmentation index were both significantly related to vascular compliance before and after stimulation with NG (Study 5). The use of quantitative assessments of common carotid artery (CCA) blood flow as an indicator of cerebral blood flow suggested the dilation of the middle cerebral artery (MCA) with NG (Study 5 and 6) and changes in MCA diameter with acute alterations in PETCO2 (Study 6). CCA and MCA velocity wave morphology were assessed showing that with changes in PETCO2, changes in CBFV velocity wave were not reflected in the CCA trace (Study 7). In addition, further assessment of the CBFV velocity trace and the calculation of CrCP and the augmentation index suggested that with changes in PETCO2 cerebrovascular compliance and cerebrovascular tension, both thought to be components of cerebrovascular tone, change independently (Study 7). Combined, the results of the presented studies suggest that changes in cerebrovascular hemodynamics can be determined from alterations in the CBFV velocity waveform morphology. However, further work is required to determine how these variations relate to specific components of cerebrovascular tone, including alterations in cerebrovascular compliance and vascular tension, and how these variables change with acute and chronic alterations in cerebrovascular hemodynamics.

Individuals with severe physical impairments have a reduced ability to communicate through movement and speech. We investigated transcranial Doppler ultrasound as a potential measurement modality for a novel brain-computer interface. It was hypothesized that cognitive activity would result in detectable changes in cerebral blood flow velocity within the middle cerebral arteries. Nine able-bodied participants alternated between rest and two different mental activities - silent word generation and mental rotation. Two analyses were performed to assess the feasibility and practicality of a TCD-based brain-computer interface. Both mental activities were independently differentiated from rest with high accuracy. Intuitive time-domain features were sufficient for classification. Data transmission rate was quadrupled by differentiating all three classes simultaneously using shorter state durations. Transcranial Doppler ultrasound can be used to automatically detect cognitive activity and may be useful as the basis of a brain-computer interface.

Individuals with severe physical impairments have a reduced ability to communicate through movement and speech. We investigated transcranial Doppler ultrasound as a potential measurement modality for a novel brain-computer interface. It was hypothesized that cognitive activity would result in detectable changes in cerebral blood flow velocity within the middle cerebral arteries. Nine able-bodied participants alternated between rest and two different mental activities - silent word generation and mental rotation. Two analyses were performed to assess the feasibility and practicality of a TCD-based brain-computer interface. Both mental activities were independently differentiated from rest with high accuracy. Intuitive time-domain features were sufficient for classification. Data transmission rate was quadrupled by differentiating all three classes simultaneously using shorter state durations. Transcranial Doppler ultrasound can be used to automatically detect cognitive activity and may be useful as the basis of a brain-computer interface.

We investigated an emerging brain-computer interface (BCI) modality, namely, transcranial Doppler ultrasonography (TCD), which measures cerebral blood flow velocity. We hypothesized that a bilateral TCD-driven online BCI would be able to dichotomously classify a user’s intentions with at least 70% accuracy. To test this hypothesis, we had three objectives: (1) to develop a signal classifier that yielded high (>80%) offline accuracies; (2) to develop an online TCD-BCI system with an onscreen keyboard; and, (3) to determine the achievable online accuracy with able-bodied participants. With a weighted, forward feature selection and a Naïve Bayes classifier, sensitivity and specificity of 81.44 ± 8.35% and 82.30 ± 7.39%, respectively, were achieved in the online differentiation of two mental tasks. The average information transfer rate and throughput of the system were 0.87 bits/min and 0.35 ± 0.18 characters/min, respectively. These promising online results encourage future testing of TCD-BCI systems with the target population.

We investigated an emerging brain-computer interface (BCI) modality, namely, transcranial Doppler ultrasonography (TCD), which measures cerebral blood flow velocity. We hypothesized that a bilateral TCD-driven online BCI would be able to dichotomously classify a user’s intentions with at least 70% accuracy. To test this hypothesis, we had three objectives: (1) to develop a signal classifier that yielded high (>80%) offline accuracies; (2) to develop an online TCD-BCI system with an onscreen keyboard; and, (3) to determine the achievable online accuracy with able-bodied participants. With a weighted, forward feature selection and a Naïve Bayes classifier, sensitivity and specificity of 81.44 ± 8.35% and 82.30 ± 7.39%, respectively, were achieved in the online differentiation of two mental tasks. The average information transfer rate and throughput of the system were 0.87 bits/min and 0.35 ± 0.18 characters/min, respectively. These promising online results encourage future testing of TCD-BCI systems with the target population.

The use of transcranial Doppler (TCD) ultrasound for the assessment of cerebral blood flow velocity (CBFV) provides an indication of cerebral blood flow assuming the diameter of the insonated vessel remains constant. Studies using TCD have traditionally described cerebrovascular hemodynamics with respect to CBFV and cerebrovascular resistance (CVRi); however, a more complete assessment of the cerebral circulation can be gleaned from the analysis of within beat characteristic of the TCD velocity waveform for the determination of cerebrovascular tone. Therefore, the general purpose of the presented studies was to assess CBFV responses and within beat characteristic for the description of cerebrovascular hemodynamics after long duration spaceflight, with sustained orthostasis, in response to changes in the partial pressure of end tidal carbon dioxide (PETCO2), and with NG stimulation. After long duration spaceflight, cerebrovascular autoregulation was found to be impaired along with a reduction in cerebrovascular CO2 reactivity (Study 1). Additionally, critical closing pressure (CrCP) was found to be increased suggesting potential remodelling of the cerebrovasculature contributing to an increase in cerebrovascular tone (Study 2). With sustained orthostasis, CBFV was found to progressively decrease and to be related to reductions in PETCO2 and increases in CrCP suggesting the contribution of changes in cerebrovascular tone leading to the development of syncope (Study 4). The CBFV reduction with the progression towards syncope was also associated with changes in waveform morphology such that the dicrotic notch point was less than the end diastolic value (Study 3). Mathematical modelling (RCKL) was used to further assess changes in cerebrovascular hemodynamics for physiological interpretation of changes in CBFV waveform morphology and found that the amplitude of the dicrotic notch and the calculation of the augmentation index were both significantly related to vascular compliance before and after stimulation with NG (Study 5). The use of quantitative assessments of common carotid artery (CCA) blood flow as an indicator of cerebral blood flow suggested the dilation of the middle cerebral artery (MCA) with NG (Study 5 and 6) and changes in MCA diameter with acute alterations in PETCO2 (Study 6). CCA and MCA velocity wave morphology were assessed showing that with changes in PETCO2, changes in CBFV velocity wave were not reflected in the CCA trace (Study 7). In addition, further assessment of the CBFV velocity trace and the calculation of CrCP and the augmentation index suggested that with changes in PETCO2 cerebrovascular compliance and cerebrovascular tension, both thought to be components of cerebrovascular tone, change independently (Study 7). Combined, the results of the presented studies suggest that changes in cerebrovascular hemodynamics can be determined from alterations in the CBFV velocity waveform morphology. However, further work is required to determine how these variations relate to specific components of cerebrovascular tone, including alterations in cerebrovascular compliance and vascular tension, and how these variables change with acute and chronic alterations in cerebrovascular hemodynamics.

No description available.

Intracranial pressure (ICP) is an important monitoring modality in the clinical management of several neurological diseases carrying the risk of fatal intracranial hypertension. However, this parameter is not always considered due to its invasive assessment. In this scenario, a non-invasive estimation of ICP (nICP) may be essential, and indeed it has become a Holy Grail in Clinical Neurosciences: extensively searched, albeit never found. This thesis is devoted to the assessment, applications and development of transcranial Doppler (TCD)-based non-invasive methods for ICP and cerebral perfusion pressure (CPP) monitoring. The thesis is divided into three sections: I) The accuracy of existing TCD-based nICP estimators in various scenarios of varying ICP (traumatic brain injury, rise of ICP during plateau waves, and rise in ICP induced by infusion of cerebrospinal fluid during infusion test). The estimators of nICP consisted of a mathematical black box model, methods based on non-invasive CPP, and a method based on TCD pulsatility index. II) The feasibility of the best performing nICP estimator in clinical practice, including patients with closed TBI and brain midline shift, patients with acute liver failure during liver transplant surgery, and patients during non-neurosurgical surgery in the beach chair position. III) The description and assessment of a novel methodology for non-invasive assessment of cerebral perfusion pressure (nCPP) based on spectral arterial blood volume accounting. As main results, TCD-based non-invasive methods could replicate changes in direct ICP across time confidently, and could provide reasonable accuracy in comparison to the standard invasive techniques. Furthermore, in feasibility studies, nICP in association with other TCD physiological parameters provided a comprehensive interpretation of cerebral haemodynamics in conditions presenting impairment of cerebral blood flow circulation. The new method of nCPP estimation could identify changes in CPP across time reliably in conditions of decreasing and increasing CPP. These findings support the use of TCD-based nICP methods in a variety of clinical conditions requiring management of ICP and brain perfusion. More importantly, the low costs associated with nICP methods, since TCD is a widely available medical device, could contribute to its widespread use as a reliable alternative for ICP monitoring in everyday clinical practice.

Introduction Cerebral autoregulation (CA) refers to the physiological mechanisms in the brain to maintain constant blood flow despite changes in cerebral perfusion pressure (CPP). It plays an important protective role against the danger of ischaemia or oedema of the brain. Over the years, various methods for CA assessment have been proposed, while most commonly used parameters include the autoregulation index (ARI), which grades CA into ten levels; transfer function (TF) analysis, describing CA as a high pass filter; the mean flow index (Mx), that estimates CA through the correlation coefficient between slow waves of mean cerebral blood flow velocity (CBFV) and CPP; and pressure reactivity index (PRx), calculated as a moving correlation coefficient between mean arterial blood pressure (ABP) and intracranial pressure (ICP). However, until now, how these parameters are related with each other is still not clear. A comprehensive investigation of the relationship between all these parameters is therefore needed. In addition, the methods mentioned above mostly assume the system being analysed is linear and the signals are stationary, with the announcement of non-stationary characteristic of CA, a more robust method, in particular suitable for non-stationary signal analysis, needs to be explored. Objectives and Methods This thesis addresses three primary questions: 1. What are the relationships between currently widely used CA parameters, i.e. Mx, ARI, TF parameters, from theoretical and practical point of view? 2. It there an effective method that can be introduced to assess CA, which is suitable for analyses of non-stationary signals? 3. How can bedside monitoring of cerebral autoregulation be improved in traumatic brain injury patients? These general aims have been translated into a series of experiments, retrospective analyses and background studies that are presented in different chapters of this thesis. Results and Conclusions This PhD project carefully scrutinised currently used CA assessment methodologies in TBI patients, demonstrating significant relationships between ARI, Mx and TF phase. A new introduced wavelet-transform-based method, wPRx was validated and showed more stable result for CA assessment than the well-established parameter, PRx. A multi-window approach with weighting system for optimal CPP estimation was described. The result showed a significant improvement in the continuity and stability of CPPopt estimation, which made it possible to be applied in the future clinical management of TBI patients.