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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.

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.

Ultrasound imaging is a ubiquitous part of the modern medical diagnostics toolbox. It has widespread applications to many areas of medicine, including angiology, cardiology, nephrology, urology, and obstetrics. It is often preferred over other imaging modalities, such as x-ray computed tomography (CAT) and magnetic resonance imaging (MRI) because it is non-invasive, non-ionizing, inexpensive, and has excellent penetration depth in the body. The design, optimization, and manufacturing of ultrasound transducers used in ultrasound imaging is a challenging engineering problem. Faced with a variety of different imaging environments, ultrasound transducers must often be optimized for performance in very specific applications. This is especially true for catheter-based solutions, such as intracardiac and intravascular ultrasound, where imaging performance is strongly dependent on the strength of backscatter from tissue due to significant limitations in device size, electronics, and signal-to-noise ratio. Currently, there is a need for the accurate and fast simulation of the imaging process used in ultrasound imaging, including the ability to capture the effects of backscatter from a variety of different tissues. This thesis discusses the development of simulation tools for the quantitative simulation of tissue backscatter and blood motion from acoustic fields coupled to spatial array transducers, based on an application of the Rayleigh speckle model to the linear systems model for acoustic diffraction from spatial array transducers. These simulation tools have potential applications in the field of medical ultrasonics, with particular attention to the areas of transducer design and optimization, beamforming and array processing, and image reconstruction. We demonstrate how the simulation tools developed here can be used to characterize array imaging performance and to investigate reconstruction performance of common flow algorithms for Doppler ultrasound imaging.

Three experiments were conducted to explore the effect of fescue toxicosis on vasoconstriction and various parameters of the estrous cycle. In the experiment of Chapter 3, a 2x2 crossover experimental design with repeated measures was implemented to test whether the ingestion of endophyte-infected tall fescue seed would alter blood hormone concentrations of prolactin, progesterone, and estradiol, interovulatory intervals, and corpus luteum blood flow. Also, Doppler ultrasonography was used to assess whether palmar artery and palmar vein lumen diameter, area, circumference, and resistivity index could be altered by the ingestion of endophyte-infected tall fescue seed. Ingestion of endophyte-infected tall fescue seed significantly decreased palmar artery resistivity index, area, and circumference, and palmar artery and palmar vein lumen diameter, but did not alter interovulatory intervals, serum concentrations of prolactin, progesterone, estradiol, or corpus luteum blood flow. Experiments 1 and 2 from Chapter 4 profiled the dopaminergic, serotonergic, and α-adrenergic receptor types and subtypes, as expressed within the equine medial palmar artery, medial palmar vein, and uterine artery transcriptomes. Combined results from Chapters 3 & 4 imply that relative quantity of serotonergic receptor subtypes within a vessel may be related to with the severity of that vessel's vasoconstrictive response to endophyte-infected tall fescue.

Cardiovascular disease, mostly atherosclerosis, is responsible for one third of all deaths globally, rising to more than 50% in the Western World. Risk factors include smoking, diet, and familial history. Doppler ultrasound can provide estimates of blood velocity and wall shear rate. Clinically, maximum velocity is used to categorise patients for surgery, although Doppler velocity measurement is prone to errors and in need of validation. Wall shear stress—which can be derived from wall shear rate—plays a role in disease initiation and progression, although its clinical utility is unclear due to difficulties associated with its measurement. This thesis investigates the use of Doppler ultrasound as a tool to estimate blood velocity and wall shear rate. A simplified method for estimation of wall shear rate in healthy arteries is developed that uses spectral Doppler ultrasound. This method is based upon the theory of oscillatory flow in rigid pipes, requiring two measurements that are readily available with clinical ultrasound machines. This method is compared to a similar method based on colour flow imaging. The spectral Doppler method underestimated the theoretic value of wall shear rate by between 7 and 22%, with results varying between phantoms. Errors for the colour method were on average 35% greater. Test measurements from one healthy volunteer demonstrated that this method can be applied in-vivo. In more advanced stages of disease, peak velocity distal to a stenosis is of clinical interest and the simplified method for wall shear rate estimation is invalid. Steady flow in a series of simplified stenosis geometries was studied using a dual-beam Doppler system to obtain velocity vectors. These measurements were compared with data from an equivalent system that used particle image velocimetry (PIV) and was considered the gold standard. For Reynolds numbers at the stenosis throat of less than 800, flow remained laminar over the region studied, although distal flow separation did occur. For higher throat Reynolds numbers—corresponding to more severe stenoses or increased flow rates—asymmetric recirculation regions developed; the transition to turbulence occurred more proximally, with a corresponding reduction in stenotic jet and recirculation length. Qualitative agreement was observed in the velocity profile shapes measured using ultrasound and PIV at throat Reynolds numbers less than 800. Above this threshold the qualitative agreement between the velocity profiles became poorer as both downstream distance and the degree of stenosis increased. Peak axial velocity distal to the stenosis was underestimated, on average, by 15% in the ultrasound system. Estimation of shear rate remained difficult with both experimental techniques. Under a Newtonian approximation, the normalised wall shear stresses agree qualitatively. Under pulsatile flow conditions using an idealised flow waveform, superior qualitative agreement was observed in the velocity profiles at diastole than at systole. Similar to the steady flow behaviour, this agreement deteriorated with stenosis severity. The current generation of clinical ultrasound machines are capable of estimating the wall shear rate in healthy arteries. In the presence of significant arterial disease, errors in the peak velocity may result in mis-selection of patients for surgery, while estimation of the wall shear stress remains extremely problematic; particularly with identifying the wall location and measuring velocities close to the wall.

Este trabalho descreve a construção e caracterização de um novo transdutor dedicado às medições susceptométricas e ultrassônicas de amostras marcadas com partículas magnéticas. Este transdutor, denominado de magnetoacústico, consiste de um sistema híbrido formado pela junção de um Biossusceptômetro de Corrente Alternada (BCA) e um transdutor ultrassônico. Seu principio básico de funcionamento consiste na medida simultânea da magnetização de um meio material marcado com partículas magnéticas e das microvibrações da estrutura interna deste meio quando excitado por um campo magnético alternado externo gerado pelas próprias bobinas de excitação do BCA. Estudos in vitro foram realizados para auxiliar no desenvolvimento e caracterização do protótipo apresentado neste trabalho. A técnica de medida empregando este transdutor híbrido foi denominada de vibromagnetoacustografia. As amostras utilizadas consistiram de meios fluidos marcados com traçadores magnéticos (micropartículas de ferrita de tamanhos variando entre 30 m e 70 m de diâmetro). Foi avaliada a dependência da resposta do sistema com diferentes parâmetros físicos tais como: viscosidade do material base o qual foi misturado as partículas ferromagnéticas; concentração dessas partículas misturadas ao material base; frequência de oscilação do campo magnético de excitação; tensão nas bobinas de excitação e a distância entre a amostra e o transdutores. A resposta do transdutor magnetoacústico apresentou melhor relação sinal/ruído em torno de 200 Hz de frequência de magnetização, considerando uma concentração de 4% de ferrita. Acima desta concentração a viscosidade do material base era alterada e interferia na medida. As respostas do susceptômetro e do ultrassom Doppler contínuo possuem uma relação linear com o nível de tensão aplicada nas bobinas de excitação e uma dependência quase linear com baixas concentrações de partículas ferromagnéticas ( 4%). Também foi realizado um teste de repetibilidade no protótipo obtendo um desvio relativo de 0,94% e 0,25% nas medições Doppler e susceptométricas, respectivamente. A medida de vibração das micropartículas ferromagnéticas realizadas in vitro, usando um transdutor Doppler contínuo, apresentou alta sensibilidade para baixas concentrações de material ferromagnético inseridos em meio fluido (~ 1%). / This work describes the construction and characterization of a new transducer dedicated to the susceptometrics and ultrasonic measurements of samples labeled with magnetic particles. This transducer, called magneto-acoustic, consists of a hybrid system formed by the junction of an Alternating Current Biosusceptometer (ACB) and an ultrasonic transducer. Its basic operation principle is the simultaneous measurement of the magnetization and the internal structure micro-vibrations of a medium labeled with magnetic particles when excited by an external alternating magnetic field generated by the ACB excitation coils. In vitro measurements were performed to support the prototype development and characterization presented in this work. The measurement technique employing this hybrid transducer was called vibromagnetoacoustography. The samples consisted of fluid medium labeled with magnetic tracers (ferrite micro particles of diameter ranging from 30 m and 70 m). It was evaluated the system response dependence with different physical parameters such as: base material viscosity in which ferromagnetic particles was mixed; the particles concentration in the base material; the oscillation frequency of the magnetic field excitation; the voltage applied on magnetizing coils and the distance between sample and transducers. The magneto-acoustic transducer response showed a better signal to noise ratio for magnetization frequency around 200 Hz and a 4% ferrite concentration. Above this concentration the base material viscosity changed disrupting the measurements. The responses of susceptometer and Doppler ultrasound have a linear dependence with the applied voltage level in the magnetizing coils and an quasi linear dependence with low ferromagnetic particles concentrations (4%). A repeatability test was also performed to the prototype which indicated a deviation of 0.94% and 0.25% in the Doppler and susceptometric measurements, respectively. The vibration measurement of ferromagnetic micro-particles performed in vitro, using a Doppler transducer, showed high sensitivity to low ferromagnetic material concentrations (~1%) immersed in a fluid medium.

The incidence of disease of the cardiovascular system is very high and increasing worldwide, especially in the developing world. The radial and ulnar arteries are implicated in some important ailments where blood flow related parameters such as flow rate (FR), wall shear rate (WSR), arterial wall motion (AWM) and pressure, all of which can be measured using ultrasound techniques, are useful in diagnosis and patient management. However these measurements are prone to error due to the manner of image formation and the complex flow conditions within the vessels. In this thesis, the errors in ultrasound-measured parameters in the radial and ulnar arteries are investigated using experimental phantoms, computer simulation and on volunteers. Using the Womersley theory, FR and WSR were estimated using a clinical ultrasound scanner with the pulsed wave (PW) mode and B mode. Experimental flow phantoms were designed to evaluate those measurements under different circumstances. A simulation technique which combined image-based computational fluid dynamics and ultrasound simulation was also used to evaluate ultrasound estimation of these parameters. A case study was then conducted on healthy volunteers to evaluate the method of measuring FR and WSR in-vivo. For the AWM in the radial artery, an auto-correlation method was used based on the radio-frequency (RF) data and validations were done by a flow phantom, simulation, and in-vivo trial. The blood pressure waveform in a volunteer’s radial artery was derived from the ultrasound measured AWM and compared with the waveform from a tonometry. FR and WSR were both found to be overestimated by up to 50%, mainly due to the beam-vessel angle in the PW Doppler ultrasound. Measurement of the vessel diameter and assumption of the blood flow direction can also influence the estimations. Other factors, such as flow amplitude, vessel size, imaging depth and flow waveforms, do not seem to affect the estimation of these two parameters. Results taken from the flow phantoms agree with those from simulation and the estimations from the in-vivo case study also agree with the published data. The auto-correlation method for the AWM was validated from the phantom and simulation. It is able to detect motion amplitude of about tens of micrometres. The trial on volunteers proved the feasibility of this motion detection method. Blood pressure waveforms at the radial artery of a volunteer, derived from this ultrasound-measured wall motion and from the tonometry, were very similar. The Womersley-based method is able to estimate the FR and WSR in the radial and ulnar arteries with high accuracy. Sources of the error and their magnitudes in estimation of the two parameters by ultrasound pointed out in this thesis are beam-vessel angle, vessel diameter measurement and flow direction assumption. Researchers and clinicians using these measurements in practice and research should be aware. The capability of ultrasound imaging to measure arterial AWM in the radial artery is demonstrated and it is found that the blood pressure waveform can also be derived from the arterial AWM.