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.

INTRODUÇÃO: O Doppler Transcraniano funcional pode avaliar mudanças na velocidade do fluxo sanguíneo encefálico associadas a tarefas cognitivas e/ou sensitivo-motoras. Mede de maneira indireta a atividade metabólica de regiões cerebrais, segundo o princípio do acoplamento neurovascular. Os objetivos deste estudo foram: desenvolver um novo método de análise de Doppler transcraniano funcional para análise da lateralização hemisférica e verificar a capacidade deste novo método em diferenciar a lateralização hemisférica durante a execução de uma tarefa motora unimanual por indivíduos saudáveis. Adicionalmente, a lateralização hemisférica foi correlacionada com a preferência manual nestes indivíduos. MÉTODOS: Treze indivíduos saudáveis foram submetidos a um exame de Doppler transcraniano funcional durante uma prova de ativação motora manual (oposição de dedos). As sessões de Doppler transcraniano funcional foram realizadas com aparelho Doppler-Box Transcranial Doppler Unit. A prova manual compreendeu uma sequência de movimentos de oposição do primeiro e segundo dedos (thumb-tofinger opposition movement) realizado por uma mão e depois pela outra, em uma frequência de 1 movimento por segundo (1Hz) fornecida por um metrônomo digital. Durante a execução dos movimentos, foram insonadas simultaneamente as artérias cerebrais médias direita e esquerda. Para interpretação dos dados de Doppler transcraniano funcional desenvolvemos um novo programa de análise denominado FDAT, que tem vantagens de sofrer mínima influência de artefatos de ruído no sinal e de não assumir um formato pré-determinado da resposta hemodinâmica cerebral. Foi calculado um índice de lateralização (IL) como a diferença entre a velocidade relativa média da época de ativação e a velocidade relativa média da época de repouso para cada prova motora. Foi calculada a diferença dos valores de IL (ILe - ILd) provenientes da análise com cada método, obtendo-se um índice de ativação, próprio de cada sujeito. A comparação do índice de ativação durante a movimentação da mão direita, e durante a movimentação da mão esquerda, foi feita com o teste de Wilcoxon. A correlação entre o índice de ativação e a preferência manual avaliada pelo Inventário de Edimburgo foi avaliada pelo coeficiente rho de Spearman. RESULTADOS: Houve uma diferença estatisticamente significante entre o IA obtido durante a movimentação da mão direita ou da mão esquerda (p=0,02). Houve correlação estatisticamente significante entre a preferência manual e a assimetria na lateralização hemisférica identificada pelo Doppler Transcraniano funcional (rho = 0.85, p < 0.001). CONCLUSÕES: A análise do Doppler Transcraniano funcional mostrou-se viável pelo método proposto, capaz de avaliar o grau de lateralização hemisférica em uma prova de ativação motora, com boa correlação com a preferência manual. Trata-se de uma ferramenta prática, não invasiva e de baixo custo para a avaliação da lateralização hemisférica em determinadas provas funcionais / INTRODUCTION: Functional transcranial Doppler is a method for the assessment of changes in blood flow velocity of the middle cerebral artery. An asymmetric increase in blood flow velocity is a marker of hemispheric lateralization during unimanual motor task performance. The aims of this study were to propose a novel and efficient method for functional transcranial Doppler analysis based on cubic smoothing splines, and to verify the ability of this method to identify hemispheric lateralization during unimanual motor task performance in healthy subjects. In addition, hemispheric lateralization was correlated with handedness in these subjects. METHODS: Thirteen healthy subjects participated in the study. Blood flow velocities in the right and left middle cerebral arteries were recorded using functional transcranial Doppler during a finger-tapping task with either the right or left hand. Data were analyzed with a multi-step new method that included: baseline determination, raw data normalization, smoothing, lateralization Index calculation, definition of rest and motor task epochs and activation Index calculation. A positive activation Index reflects right-hemisphere lateralization and a negative activation index, left hemisphere lateralization. RESULTS: There was a statistically significant difference between the activation index obtained during right or left hand movements (p=0.02). Hand dominance was significantly correlated with asymmetry in hemispheric lateralization assessed with functional transcranial Doppler (rho = 0.85, p<0.001). CONCLUSIONS: This novel method for functional transcranial Doppler analysis was capable to assess the hemispheric lateralization during motor task performance, and correlated well with handedness. It is a practical, non-invasive and unexpensive tool for the assessment of hemispheric lateralization.

INTRODUÇÃO: O Doppler Transcraniano funcional pode avaliar mudanças na velocidade do fluxo sanguíneo encefálico associadas a tarefas cognitivas e/ou sensitivo-motoras. Mede de maneira indireta a atividade metabólica de regiões cerebrais, segundo o princípio do acoplamento neurovascular. Os objetivos deste estudo foram: desenvolver um novo método de análise de Doppler transcraniano funcional para análise da lateralização hemisférica e verificar a capacidade deste novo método em diferenciar a lateralização hemisférica durante a execução de uma tarefa motora unimanual por indivíduos saudáveis. Adicionalmente, a lateralização hemisférica foi correlacionada com a preferência manual nestes indivíduos. MÉTODOS: Treze indivíduos saudáveis foram submetidos a um exame de Doppler transcraniano funcional durante uma prova de ativação motora manual (oposição de dedos). As sessões de Doppler transcraniano funcional foram realizadas com aparelho Doppler-Box Transcranial Doppler Unit. A prova manual compreendeu uma sequência de movimentos de oposição do primeiro e segundo dedos (thumb-tofinger opposition movement) realizado por uma mão e depois pela outra, em uma frequência de 1 movimento por segundo (1Hz) fornecida por um metrônomo digital. Durante a execução dos movimentos, foram insonadas simultaneamente as artérias cerebrais médias direita e esquerda. Para interpretação dos dados de Doppler transcraniano funcional desenvolvemos um novo programa de análise denominado FDAT, que tem vantagens de sofrer mínima influência de artefatos de ruído no sinal e de não assumir um formato pré-determinado da resposta hemodinâmica cerebral. Foi calculado um índice de lateralização (IL) como a diferença entre a velocidade relativa média da época de ativação e a velocidade relativa média da época de repouso para cada prova motora. Foi calculada a diferença dos valores de IL (ILe - ILd) provenientes da análise com cada método, obtendo-se um índice de ativação, próprio de cada sujeito. A comparação do índice de ativação durante a movimentação da mão direita, e durante a movimentação da mão esquerda, foi feita com o teste de Wilcoxon. A correlação entre o índice de ativação e a preferência manual avaliada pelo Inventário de Edimburgo foi avaliada pelo coeficiente rho de Spearman. RESULTADOS: Houve uma diferença estatisticamente significante entre o IA obtido durante a movimentação da mão direita ou da mão esquerda (p=0,02). Houve correlação estatisticamente significante entre a preferência manual e a assimetria na lateralização hemisférica identificada pelo Doppler Transcraniano funcional (rho = 0.85, p < 0.001). CONCLUSÕES: A análise do Doppler Transcraniano funcional mostrou-se viável pelo método proposto, capaz de avaliar o grau de lateralização hemisférica em uma prova de ativação motora, com boa correlação com a preferência manual. Trata-se de uma ferramenta prática, não invasiva e de baixo custo para a avaliação da lateralização hemisférica em determinadas provas funcionais / INTRODUCTION: Functional transcranial Doppler is a method for the assessment of changes in blood flow velocity of the middle cerebral artery. An asymmetric increase in blood flow velocity is a marker of hemispheric lateralization during unimanual motor task performance. The aims of this study were to propose a novel and efficient method for functional transcranial Doppler analysis based on cubic smoothing splines, and to verify the ability of this method to identify hemispheric lateralization during unimanual motor task performance in healthy subjects. In addition, hemispheric lateralization was correlated with handedness in these subjects. METHODS: Thirteen healthy subjects participated in the study. Blood flow velocities in the right and left middle cerebral arteries were recorded using functional transcranial Doppler during a finger-tapping task with either the right or left hand. Data were analyzed with a multi-step new method that included: baseline determination, raw data normalization, smoothing, lateralization Index calculation, definition of rest and motor task epochs and activation Index calculation. A positive activation Index reflects right-hemisphere lateralization and a negative activation index, left hemisphere lateralization. RESULTS: There was a statistically significant difference between the activation index obtained during right or left hand movements (p=0.02). Hand dominance was significantly correlated with asymmetry in hemispheric lateralization assessed with functional transcranial Doppler (rho = 0.85, p<0.001). CONCLUSIONS: This novel method for functional transcranial Doppler analysis was capable to assess the hemispheric lateralization during motor task performance, and correlated well with handedness. It is a practical, non-invasive and unexpensive tool for the assessment of hemispheric lateralization.

Introdução: O ultrassom transcraniano colorido (UTCC) é uma técnica ultrassonográfica que incorpora a imagem do parênquima cerebral à avaliação do fluxo sanguíneo dos vasos do polígono de Willis. Uma de suas maiores limitações é a necessidade de uma janela transtemporal adequada para insonação transcraniana, o que está ausente em cerca de 5-44% dos pacientes. A hiperostose da escama temporal tem sido fortemente associada a falência de janela transtemporal. Objetivamos neste estudo observacional analítico, avaliar a relação entre a a qualidade da janela transtemporal determinada com o UTCC e as características do osso temporal determinada com a tomografia computadorizada de crânio (TC). Materiais e métodos: Trata-se de estudo retrospectivo, analítico, observacional com avaliação de registros médicos onde foram incluídos para análise um total de 187 pacientes com acidente vascular cerebral ou AIT admitidos na Unidade de Emergência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto entre Julho de 2014 e Janeiro de 2015 que realizaram UTCC e TC de acordo com o protocolo institucional. Classificamos a qualidade das janelas dos pacientes com um escore validado em nosso serviço. A análise da espessura e densidade do osso temporal nos exames de TC foi realizada de forma cega para os demais dados clínicos e ultrassonográficos. Resultados: Ausência de Janela temporal bilateral foi encontrada em 21,93% dos pacientes da amostra e destes pacientes (78,05%) foram do sexo feminino p value < 0,0001. A média de idade dos pacientes com presença de Janela temporal foi de 59,9±13,9 anos e as medias de idade dos pacientes sem janela temporal foi de 70,5±12,7 anos com p value <0,001. A área sob a curva ROC para acurácia diagnóstica na detecção de ausência de janela a partir da espessura da escama temporal foi de 0,8232 (0,7504; 0,896) e para o ponto de corte de espessura da escama temporal na ROI de 2,23mm encontramos uma sensibilidade de 0,878 e especificidade de 0,537; Em uma regressão logística univariada, obtivemos que para cada 1 mm de aumento na espessura do osso temporal, obtivemos Odds Ratio (OR) de 4,16 em não se obter janela transtemporal pelo UTCC. Em uma regressão logística multivariada, a espessura da escama temporal em mm (OR : 3,04; IC95%: 1,73-5,35; p: 0,001) idade (OR de 1,07; IC95%: 1,03-1,11; p: 0,003) sexo feminino (OR: 5,99 IC95%:2,09-17,15; p: 0,009) se associaram com ausência da janela transtemporal e a presença de pneumatização óssea na escama do osso temporal (OR: 7,90; IC95%: 1,94-32,04; p: 0,003) se associou com presença da janela transtemporal. Discussão e conclusão: Em concordância com estudos prévios de DTC, os resultados encontrados com a técnica de UTCC sugerem que mulheres idosas possuem maior espessura da escama temporal e por consequência maior taxa de falência de janela transtemporal. Maior espessura do osso temporal e presença de pneumatização do osso temporal são fatores independentes que aumentam a chance de falência de janela transtemporal. A partir da espessura do osso temporal é possível prever a falência de janela transtemporal e assim identificar pacientes elegíveis para a realização do UTCC ou DTC / Introduction: Transcranial color Doppler ultrasound (TCDU) is an ultrasonographic technique that incorporates the image of the cerebral parenchyma to evaluate blood flow in the vessels of the Willis polygon. One of its major limitations is the need for a transtemporal window suitable for transcranial insonation, which is absent in about 5-44% of patients. Hyperostosis of the temporal scale has been strongly associated with transtemporal window failure. In this analytical observational study, we aimed to evaluate the association between the quality of the transtemporal window determined with the TCDU and the characteristics of the temporal bone determined by cranial computed tomography (CT). Materials and methods: This was a retrospective, analytical, observational study with evaluation of medical records where a total of 187 patients with stroke or TIA admitted to the Emergency Unit of the Hospital das Clínicas of the Medical School of Ribeirão Preto between July 2014 and January 2015 who underwent TCDU and CT according to the institutional protocol. We rated the quality of patients\' windows with a score validated at our service. Analysis of temporal bone thickness and density on CT scans was performed blindly for other clinical and ultrasonographic data. Results: Absence of bilateral temporal window was found in 21.93% of the patients in the sample and of these patients 78.05% were female p value <0.0001. The mean age of the patients with presence of temporal window was 59.9 ± 13.9 years and the mean age of patients without temporal window was 70.5 ± 12.7 years with p value <0.001. The area under the ROC curve for diagnostic accuracy in the detection of window absence, from the thickness of the temporal bone, was 0.8232 IC 95% (0.7504; 0.896) and for the cutoff point of the temporal scale thickness at ROI of 2.23mm we found a sensitivity of 0.878 and Specificity of 0.537; In a univariate logistic regression, we found that for each 1 mm of increase in temporal bone thickness, there was an odds ratio (OR) of 4.16 of not being able to obtain a transtemporal window by the TCDU. In a univariate logistic regression, we found that for each 1 mm increase in thickness of the temporal bone, obtained odds ratio (OR) of 4.16 to not obtain transtemporal window by the TCDU. In a multivariate logistic regression, the thickness in mm of the temporal scale (OR: 3.04; 95% CI: 1.73 to 5.35; p: 0.001), age (OR 1.07; 95% CI: 1,03 to 1.11, p: 0.003), being female (OR 5.99 95% CI: 2.09 to 17.15, P: 0.009) were associated with the absence of the transtemporal window, and the presence of bone pneumatized scale in the temporal region (OR: 7.90; 95% CI: 1.94 to 32.04, P: 0.003) was associated with the absence of the transtemporal window. Discussion and conclusion: In agreement with previous TCD studies, we have found that older women have a greater thickness of temporal scales and, consequently, a higher rate of transtemporal window failure on TCDU. From temporal bone thickness it is possible to predict transtemporal window failure and therefore to predict those patients with acute stroke that are suitable for UTCC or TCD exams.

Introdução: O ultrassom transcraniano colorido (UTCC) é uma técnica ultrassonográfica que incorpora a imagem do parênquima cerebral à avaliação do fluxo sanguíneo dos vasos do polígono de Willis. Uma de suas maiores limitações é a necessidade de uma janela transtemporal adequada para insonação transcraniana, o que está ausente em cerca de 5-44% dos pacientes. A hiperostose da escama temporal tem sido fortemente associada a falência de janela transtemporal. Objetivamos neste estudo observacional analítico, avaliar a relação entre a a qualidade da janela transtemporal determinada com o UTCC e as características do osso temporal determinada com a tomografia computadorizada de crânio (TC). Materiais e métodos: Trata-se de estudo retrospectivo, analítico, observacional com avaliação de registros médicos onde foram incluídos para análise um total de 187 pacientes com acidente vascular cerebral ou AIT admitidos na Unidade de Emergência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto entre Julho de 2014 e Janeiro de 2015 que realizaram UTCC e TC de acordo com o protocolo institucional. Classificamos a qualidade das janelas dos pacientes com um escore validado em nosso serviço. A análise da espessura e densidade do osso temporal nos exames de TC foi realizada de forma cega para os demais dados clínicos e ultrassonográficos. Resultados: Ausência de Janela temporal bilateral foi encontrada em 21,93% dos pacientes da amostra e destes pacientes (78,05%) foram do sexo feminino p value < 0,0001. A média de idade dos pacientes com presença de Janela temporal foi de 59,9±13,9 anos e as medias de idade dos pacientes sem janela temporal foi de 70,5±12,7 anos com p value <0,001. A área sob a curva ROC para acurácia diagnóstica na detecção de ausência de janela a partir da espessura da escama temporal foi de 0,8232 (0,7504; 0,896) e para o ponto de corte de espessura da escama temporal na ROI de 2,23mm encontramos uma sensibilidade de 0,878 e especificidade de 0,537; Em uma regressão logística univariada, obtivemos que para cada 1 mm de aumento na espessura do osso temporal, obtivemos Odds Ratio (OR) de 4,16 em não se obter janela transtemporal pelo UTCC. Em uma regressão logística multivariada, a espessura da escama temporal em mm (OR : 3,04; IC95%: 1,73-5,35; p: 0,001) idade (OR de 1,07; IC95%: 1,03-1,11; p: 0,003) sexo feminino (OR: 5,99 IC95%:2,09-17,15; p: 0,009) se associaram com ausência da janela transtemporal e a presença de pneumatização óssea na escama do osso temporal (OR: 7,90; IC95%: 1,94-32,04; p: 0,003) se associou com presença da janela transtemporal. Discussão e conclusão: Em concordância com estudos prévios de DTC, os resultados encontrados com a técnica de UTCC sugerem que mulheres idosas possuem maior espessura da escama temporal e por consequência maior taxa de falência de janela transtemporal. Maior espessura do osso temporal e presença de pneumatização do osso temporal são fatores independentes que aumentam a chance de falência de janela transtemporal. A partir da espessura do osso temporal é possível prever a falência de janela transtemporal e assim identificar pacientes elegíveis para a realização do UTCC ou DTC / Introduction: Transcranial color Doppler ultrasound (TCDU) is an ultrasonographic technique that incorporates the image of the cerebral parenchyma to evaluate blood flow in the vessels of the Willis polygon. One of its major limitations is the need for a transtemporal window suitable for transcranial insonation, which is absent in about 5-44% of patients. Hyperostosis of the temporal scale has been strongly associated with transtemporal window failure. In this analytical observational study, we aimed to evaluate the association between the quality of the transtemporal window determined with the TCDU and the characteristics of the temporal bone determined by cranial computed tomography (CT). Materials and methods: This was a retrospective, analytical, observational study with evaluation of medical records where a total of 187 patients with stroke or TIA admitted to the Emergency Unit of the Hospital das Clínicas of the Medical School of Ribeirão Preto between July 2014 and January 2015 who underwent TCDU and CT according to the institutional protocol. We rated the quality of patients\' windows with a score validated at our service. Analysis of temporal bone thickness and density on CT scans was performed blindly for other clinical and ultrasonographic data. Results: Absence of bilateral temporal window was found in 21.93% of the patients in the sample and of these patients 78.05% were female p value <0.0001. The mean age of the patients with presence of temporal window was 59.9 ± 13.9 years and the mean age of patients without temporal window was 70.5 ± 12.7 years with p value <0.001. The area under the ROC curve for diagnostic accuracy in the detection of window absence, from the thickness of the temporal bone, was 0.8232 IC 95% (0.7504; 0.896) and for the cutoff point of the temporal scale thickness at ROI of 2.23mm we found a sensitivity of 0.878 and Specificity of 0.537; In a univariate logistic regression, we found that for each 1 mm of increase in temporal bone thickness, there was an odds ratio (OR) of 4.16 of not being able to obtain a transtemporal window by the TCDU. In a univariate logistic regression, we found that for each 1 mm increase in thickness of the temporal bone, obtained odds ratio (OR) of 4.16 to not obtain transtemporal window by the TCDU. In a multivariate logistic regression, the thickness in mm of the temporal scale (OR: 3.04; 95% CI: 1.73 to 5.35; p: 0.001), age (OR 1.07; 95% CI: 1,03 to 1.11, p: 0.003), being female (OR 5.99 95% CI: 2.09 to 17.15, P: 0.009) were associated with the absence of the transtemporal window, and the presence of bone pneumatized scale in the temporal region (OR: 7.90; 95% CI: 1.94 to 32.04, P: 0.003) was associated with the absence of the transtemporal window. Discussion and conclusion: In agreement with previous TCD studies, we have found that older women have a greater thickness of temporal scales and, consequently, a higher rate of transtemporal window failure on TCDU. From temporal bone thickness it is possible to predict transtemporal window failure and therefore to predict those patients with acute stroke that are suitable for UTCC or TCD exams.

Early deterioration and long-term recurrence were common after stroke or transient ischemic attach (TIA), however, it is unclear whether they were correlated with active embolization and the consequent new cerebral infarct in acute phase. By employing TCD and diffusion weighted imaging (DWI), we studied the significance of the progression of MES and infarcts during acute phase on the clinical outcomes. We found that the disappearance of MES was correlated with better improvement on day 7 of recruitment; for the long-term outcome, occurrence of exacerbating infarct tended to predict recurrent stroke. Treatment aiming to reduce MES and prevent infarct exacerbation in acute phase may improve the prognosis after stroke. / Finally, one study was performed to assess the changes of hemodynamic parameters after stenting of severe stenosis in the MCA. We aimed to investigate whether TCD can reflect the lumen changes after revascularization and detect hyperperfusion. The findings showed that the velocity of stented MCA in most patients normalized within 24 hours after procedure, but the role of TCD in detecting restenosis in long run needed to be verified; no one suffered from hyperperfusion during the period of our study. The long-term outcomes of patients with normalized velocity versus those with persistently high velocity needed to be further studied. Apart from the velocity changes, changes of the collateral flow after intervention may also be an important part of hemodynamic changes. (Abstract shortened by UMI.) / It was suggested that anti-platelet therapy can reduce the MES, but little was known about the efficacy of low molecular weight heparin (LMWH) although in theory LMWH can reduce the red fibrin-dependent thromboemboli. As a sub-analysis of Fraxiparine in Ischemic Stroke (FISS)-tris study, our study did not show advantages of LMWH in eliminating MES compared with aspirin. / Previous studies showed the accuracy of TCD in diagnosis of middle cerebral artery (MCA) stenosis was variable and the positive predictive value (PPV) was less than 50% in a recent report. One of the important reasons was that most criteria were based on the velocity-only method, ignoring other non-velocity information. Thus, we tried to establish new diagnostic criteria by means of designing an assessment form which integrated more characteristics apart from the velocity acceleration. A composite score for each MCA was calculated according to following parameters in the form: Velocity Scale (score 0-6 for peak systolic velocities&lt;140 to &ge;300cm/s), Hemodynamic Scale (score 0-5 for focal or diffuse velocity increase; score 0-6 for differences between bilateral MCA; score 17 for damping velocity), Spectrum Scale (score 0-2 for normal spectrum, turbulence and musical murmurs). Our results showed that compared with the previously reported criteria, the score calculated from the assessment form yielded much more balanced accuracy against magnetic resonance angiography (MRA) and digital subtraction angiography (DSA). However, the composition of the assessment form was only based on personal experience and need to be further modified. Multicenter studies with large sample size are also needed to confirm the advantages of this new method. / Second, we performed three studies to investigate the relationship between the progression of MES and the short or long-term outcome and the relationship between MES and different treatments. / Hao, Qing. / Adviser: Ka Sing Wong. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3419. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 155-181). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Brain diseases including neurological disorders and tumors remain undertreated due to the challenge in accessing the brain, and blood-brain barrier (BBB) restricting drug delivery, which also profoundly limits the development of pharmacological treatment. Focused ultrasound (FUS) with acoustic agents including microbubbles and nanodroplets remains as the only method to open the BBB noninvasively, locally, and transiently to assist drug delivery. For an ideal medical system to serve a broad patient population, it requires precise and flexible targeting with simulation to personalize treatment, real-time monitoring to ensure safety and effectiveness, and rapid application, as repetitive pharmacological treatment is often required. Since none of current systems fulfills all the requirements, here we designed a neuronavigation-guided FUS system with protocol assessed in in vivo mice, in vivo non-human primates, and human skulls from in silico preplanning, online FUS treatment and real-time acoustic monitoring and mapping, to post-treatment assessment using MRI. Both sedate and awake non-human primates were evaluated with total treatment time averaging 30 min and 3-mm targeting accuracy in cerebral cortex and subcortical structures. The FUS system developed would enable transcranial FUS in patients with high accuracy and independent of MRI guidance.

Functional neuroimaging techniques such as near-infrared spectroscopy (NIRS) have been studied in brain-computer interface (BCI) development. Previous research has suggested that the addition of a second brain-monitoring modality may improve the accuracy of a NIRS-BCI. The objective of this study was to determine whether the classification accuracies achievable by a multimodal BCI, which combines NIRS and transcranial Doppler ultrasonography (TCD) signals, can exceed those attainable using a unimodal NIRS-BCI or TCD-BCI. Nine able-bodied subjects participated in the study. Simultaneous measurements were made with NIRS and TCD instruments while participants were prompted to perform a verbal fluency task or to remain at rest, within the context of a block-stimulus paradigm. In five of nine (55.6%) participants, classification accuracies with the NIRS-TCD system were significantly higher (p<0.05) than with NIRS or TCD systems alone. Our results suggest that multimodal neuroimaging may be a promising approach towards improving the accuracy of future BCIs.

Functional neuroimaging techniques such as near-infrared spectroscopy (NIRS) have been studied in brain-computer interface (BCI) development. Previous research has suggested that the addition of a second brain-monitoring modality may improve the accuracy of a NIRS-BCI. The objective of this study was to determine whether the classification accuracies achievable by a multimodal BCI, which combines NIRS and transcranial Doppler ultrasonography (TCD) signals, can exceed those attainable using a unimodal NIRS-BCI or TCD-BCI. Nine able-bodied subjects participated in the study. Simultaneous measurements were made with NIRS and TCD instruments while participants were prompted to perform a verbal fluency task or to remain at rest, within the context of a block-stimulus paradigm. In five of nine (55.6%) participants, classification accuracies with the NIRS-TCD system were significantly higher (p<0.05) than with NIRS or TCD systems alone. Our results suggest that multimodal neuroimaging may be a promising approach towards improving the accuracy of future BCIs.

No description available.