Radio frequency (RF) lesioning and deep brain stimulation (DBS) are the two prevailing surgical treatments for movement disorders within the field of stereotactic and functional neurosurgery. For RF-lesioning, a small volume of brain tissue is coagulated and knowledge of the lesion size and growth is of great importance for the safety and outcome of the procedure. This thesis deals with adapting the laser Doppler perfusion monitoring (LDPM) technique for measurements in brain tissue during RF-lesioning. The relation between LDPM signal changes and developed lesion size was investigated. LDPM measurements were evaluated both in vitro (albumin protein solution) and in vivo in the porcine brain during RF-lesioning corresponding to a bilateral thalamotomy in man. The investigated signals from the LDPI measurements can be used for following the lesioning time course and to detect if a lesion was created, both in vitro and in the animal model. For the albumin model, both the total backscattered light intensity and the perfusion signal can be used as markers for estimating the final coagulation size, while in the animal model this conclusion was not statistical verified. Independent on surgical method, RF-lesioning or DBS, intracerebral guidance is an important aspect within stereotactic and functional neurosurgery. To increase the accuracy and precision of reaching the correct target, different methods for intracerebral guidance exist, such as microelectrode recording and impedance methods. In this thesis, the possibility of developing an optical intracerebral guidance method has been investigated. Diffuse reflectance spectroscopy served as technology and all measurements were performed stereotactically in both porcine and human brain. Measurements of white and gray matter showed large differences, with higher reflectivity for white brain matter, both in porcine and in human brain. For the human measurements during DBS-implants, large differences between white matter and functional targets were found. Additionally, differences between native and lesioned porcine brain matter were detected. Both studies support the idea of using diffuse reflectance spectroscopy for developing an intracerebral guidance method.

Coronary artery bypass graft (CABG) surgery is a common treatment for patients with coronary artery disease. A potential complication of CABG is myocardial ischemia or infarction. In this thesis, a method - based on laser Doppler flowmetry (LDF) - for detection of intra- and postoperative ischemia by myocardial perfusion monitoring is evaluated. LDF is sensitive to motion artifacts. In previous studies, a method for reduction of motion artifacts when measuring on the beating heart has been developed. By using the ECG as a reference, the perfusion signal is measured in intervals during the cardiac cycle where the cardiac motion is at a minimum, thus minimizing the artifacts in the perfusion signal. The aim of this thesis was to investigate the possibilities to use the ECG-triggered laser Doppler system for continuous monitoring of myocardial perfusion in humans during and after CABG surgery. Two studies were performed. In the first study, changes in myocardial perfusion during CABG surgery were investigated (n = 13), while the second study focused on postoperative measurements (n = 13). In addition, an ECG-triggering method was implemented and evaluated. It was found that the large variations in myocardial perfusion during CABG surgery could be monitored with the ECG-triggered laser Doppler system. Furthermore, a perfusion signal of good quality could be registered postoperatively from the closed chest in ten out of thirteen patients. In eight out of ten patients, a proper signal was obtained also the following morning, i.e., about 20 hours after probe insertion. The results show that respiration and blood pressure can have an influence on the perfusion signal. In conclusion, the results indicate that the method is able to detect fluctuations in myocardial perfusion under favourable circumstances. However, high heart rate, abnormal cardiac motion, improper probe attachment and limitations in the ECG-triggering method may result in variations in the perfusion signal that are not related to tissue perfusion. / Varje år utförs omkring 4500 kranskärlsoperationer i Sverige. En allvarlig komplikation som kan uppstå efter operationen är otillräcklig blodförsörjning till hjärtmuskeln. Den här licentiatavhandlingen handlar om utveckling och utvärdering av en metod, baserad på laserdopplerteknik, för att kunna upptäcka nedsatt blodperfusion i hjärtmuskeln på ett tidigt stadium. Laserdopplertekniken är känslig för rörelsestörningar. I tidigare studier har en metod för reducering av rörelsestörningar vid mätning på slående hjärta tagits fram. Med EKG:t som referens mäts blodperfusionen i de faser under hjärtcykeln då hjärtats rörelse är som minst, vilket minskar bidraget av rörelsestörningar i blodperfusionssignalen. I den här avhandlingen undersöks om metoden kan användas för kontinuerlig övervakning av hjärtmuskelns blodperfusion på patienter under och efter hjärtoperationer. Två studier har genomförts: en där hjärtmuskelns perfusion mättes i olika faser under kranskärlsoperationer och en där mätproben lades in i hjärtmuskeln under operationen och mätningar gjordes under det första dygnet efter operationen. Det visade sig vara möjligt att följa förändringar i hjärtmuskelns blodperfusion under operation. Det var även möjligt att registrera en perfusionssignal av god kvalitet efter operationen då bröstkorgen var stängd. Hos åtta av tio patienter erhölls en bra signal även morgonen efter operationen, dvs. ca 20 timmar efter att proben lades in. Resultaten visar också att andning och blodtryck kan ha en påverkan på blodperfusionssignalen. Slutsatsen av arbetet är att det går att se variationer i hjärtmuskelns blodperfusion med EKG-triggad laserdoppler under vissa förutsättningar. Signalen är dock i många fall svårtolkad på grund av att t ex hög hjärtfrekvens, onormal hjärtväggsrörelse eller ändrad probposition sannolikt kan ge variationer i perfusionssignalen som inte är relaterade till blodflödesförändringar. / Report code: LIU-TEK-LIC-2007:35.

<p>Coronary artery bypass graft (CABG) surgery is a common treatment for patients with coronary artery disease. A potential complication of CABG is myocardial ischemia or infarction. In this thesis, a method - based on laser Doppler flowmetry (LDF) - for detection of intra- and postoperative ischemia by myocardial perfusion monitoring is evaluated.</p><p>LDF is sensitive to motion artifacts. In previous studies, a method for reduction of motion artifacts when measuring on the beating heart has been developed. By using the ECG as a reference, the perfusion signal is measured in intervals during the cardiac cycle where the cardiac motion is at a minimum, thus minimizing the artifacts in the perfusion signal.</p><p>The aim of this thesis was to investigate the possibilities to use the ECG-triggered laser Doppler system for continuous monitoring of myocardial perfusion in humans during and after CABG surgery. Two studies were performed. In the first study, changes in myocardial perfusion during CABG surgery were investigated (n = 13), while the second study focused on postoperative measurements (n = 13). In addition, an ECG-triggering method was implemented and evaluated.</p><p>It was found that the large variations in myocardial perfusion during CABG surgery could be monitored with the ECG-triggered laser Doppler system. Furthermore, a perfusion signal of good quality could be registered postoperatively from the closed chest in ten out of thirteen patients. In eight out of ten patients, a proper signal was obtained also the following morning, i.e., about 20 hours after probe insertion. The results show that respiration and blood pressure can have an influence on the perfusion signal.</p><p>In conclusion, the results indicate that the method is able to detect fluctuations in myocardial perfusion under favourable circumstances. However, high heart rate, abnormal cardiac motion, improper probe attachment and limitations in the ECG-triggering method may result in variations in the perfusion signal that are not related to tissue perfusion.</p> / <p>Varje år utförs omkring 4500 kranskärlsoperationer i Sverige. En allvarlig komplikation som kan uppstå efter operationen är otillräcklig blodförsörjning till hjärtmuskeln. Den här licentiatavhandlingen handlar om utveckling och utvärdering av en metod, baserad på laserdopplerteknik, för att kunna upptäcka nedsatt blodperfusion i hjärtmuskeln på ett tidigt stadium.</p><p>Laserdopplertekniken är känslig för rörelsestörningar. I tidigare studier har en metod för reducering av rörelsestörningar vid mätning på slående hjärta tagits fram. Med EKG:t som referens mäts blodperfusionen i de faser under hjärtcykeln då hjärtats rörelse är som minst, vilket minskar bidraget av rörelsestörningar i blodperfusionssignalen.</p><p>I den här avhandlingen undersöks om metoden kan användas för kontinuerlig övervakning av hjärtmuskelns blodperfusion på patienter under och efter hjärtoperationer. Två studier har genomförts: en där hjärtmuskelns perfusion mättes i olika faser under kranskärlsoperationer och en där mätproben lades in i hjärtmuskeln under operationen och mätningar gjordes under det första dygnet efter operationen.</p><p>Det visade sig vara möjligt att följa förändringar i hjärtmuskelns blodperfusion under operation. Det var även möjligt att registrera en perfusionssignal av god kvalitet efter operationen då bröstkorgen var stängd. Hos åtta av tio patienter erhölls en bra signal även morgonen efter operationen, dvs. ca 20 timmar efter att proben lades in. Resultaten visar också att andning och blodtryck kan ha en påverkan på blodperfusionssignalen.</p><p>Slutsatsen av arbetet är att det går att se variationer i hjärtmuskelns blodperfusion med EKG-triggad laserdoppler under vissa förutsättningar. Signalen är dock i många fall svårtolkad på grund av att t ex hög hjärtfrekvens, onormal hjärtväggsrörelse eller ändrad probposition sannolikt kan ge variationer i perfusionssignalen som inte är relaterade till blodflödesförändringar.</p> / Report code: LIU-TEK-LIC-2007:35.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A disfunção endotelial tem sido sugerida como evento precoce na patogênese das complicações vasculares do DM1. O presente estudo objetivou avaliar a função endotelial na microcirculação e rigidez arterial no diabetes tipo 1 comparando com controles não diabéticos e correlacionando com variáveis clínicas, demográficas e laboratoriais. Foram avaliados 57 pacientes com diabetes tipo 1 com idade de 32,5 (13-61) anos e duração de doença de 15 (1-48) anos e 53 controles através de fluxometria cutânea por laser-Doppler após iontoforese de Acetilcolina(ACh) (resposta endotélio dependente), hiperemia reativa pós oclusiva(HRPO) e a capacidade máxima de vasodilatação após hiperemia térmica. Já a resposta endotélio independente foi avaliada após iontoforese de Nitroprussiato de sódio (NPS). A rigidez arterial foi mensurada através da análise da onda de pulso digital com os índices de rigidez arterial e de reflexão. Os pacientes diabéticos foram submetidos à avaliação clínica e laboratorial (histórico de tabagismo, dose diária de insulina, duração do diabetes, uso de drogas que alteram a função endotelial como anti-hipertensivos e estatinas, níveis pressóricos, índice de massa corporal, excreção urinária de albumina, perfil lipídico, controle glicêmico e níveis de proteína C-reativa). O fluxo microvascular médio em repouso não foi diferente entre pacientes e controles , assim como a complacência arterial mensurada através do índice de rigidez arterial e do índice de reflexão. A resposta vascular a vasodilatação mediada pela ACh encontrou-se significantemente reduzida nos pacientes (p=0,002). No entanto, apesar da diferença verificada na área abaixo da curva de NPS em relação ao controle, a análise por medidas repetidas não apontou diferença entre os grupos em relação às doses entre os grupos (p=0,15). A vasodilatação cutânea máxima induzida pela hiperemia térmica foi maior entre os controles em comparação com os diabéticos &#61677;93,6(24,5-379-,9) e 56,6(31,5-204,5), respectivamente p=0,04&#61693;. Por outro lado, durante a HRPO, o aumento máximo no fluxo e a área abaixo da resposta hiperêmica não divergiram entre pacientes e controles, embora o tempo para alcançar o fluxo máximo tenha sido maior nos diabéticos do que nos controles(p=0,02). As principais variáveis correlacionadas com a microcirculação foram o ácido úrico, a hemoglobina glicada, a idade e a proteína C reativa, e com a rigidez arterial, foram a duração do Diabetes, a Pressão arterial diastólica e o HDL. Apesar da correlação entre o uso de drogas com propriedades hemorreológicas e a rigidez arterial, a exclusão dos pacientes usuários daqueles medicamentos não alterou os resultados obtidos. Concluímos que, na população de diabéticos tipo 1 estudada, a resposta vascular endotélio dependente, e a capacidade máxima de vasodilatação estão significativamente reduzidas. Não houve diferença entre diabéticos e controles quanto à rigidez arterial. Ademais, a vasodilatação microcirculatória mediada pela Acetilcolina pode ser correlacionada com a rigidez arterial em diabéticos. Estudos posteriores devem ser realizados no intuito de avaliar a influência exercida pelas drogas que alteram a função endotelial sobre a reatividade micro e macrovascular. / Endothelial dysfunction in patients with type 1 diabetes appears to be an early event in the genesis of vascular complications. The purpose of the present study is to assess endothelial function in the microcirculation and arterial stiffness, by comparing with non-diabetic controls, and correlating with clinical, demographic and laboratorial parameters. We evaluated 57 patients with type 1 diabetes aged 32.5 (13-61) years and with a disease duration of 15 (1-48)years, and 53 controls using laser Doppler flowmetry during low-current iontophoresis of acetylcholine (ACh) (endothelium dependent response), post occlusive reactive hyperemia(PORH) and maximum vasodilator function during thermal hyperemia. Endothelium-independent response was measured after iontophoresis of sodium nitroprusside (SNP).The peripheral pressure waveform was analyzed to assess the arterial stiffness. Diabetic patients underwent clinical and laboratory evaluation (smoking, disease duration, daily insulin dose, use of medications that could improve endothelial function such as antihypertensive drugs and statins, blood pressure, body mass index, urinary albumin excretion, lipid profile, glycemic control and C-reactive protein levels-CRP). Mean resting microvascular flux did not differ between control subjects and patients with type 1 diabetes, as well as arterial stiffness assessed through stiffness index and reflection index. Microvascular response to ACh was significantly reduced in patients (p=0,002). However, despite the reduction ofAUC NPS, the analysis with repeated measures disclosed no difference between the groups in relation to the doses (p=0,15). Maximal skin microvascular vasodilation induced by thermal hyperemia was found to be higher in the control group than among patients (&#61677;93,6(24,5-379-,9) e 56,6(31,5-204,5), respectively p=0,04). On the other hand, during PORH, maximal increase in flux and area under the curve of the hyperemic response did not differ between patients and controls, although the time frame to reach maximum flux and the time to half recovery after hyperemia was longer in patients than in controls (P=0.02) . Uric acid, hba1c, age and CRP were the most important contributing factors to the variation of microvascular reactivity, while disease duration, the diastolic arterial pressure and HDL cholesterol were independently associated to arterial stiffness. Despite the correlation between drugs with hemorheologycal properties and arterial stiffness, the exclusion of patients who were taking such substances did not affect the results. We conclude that in the studied population of type 1 diabetic patients, the endothelium-dependent vascular responses and maximal vasodilator capacity are significantly reduced. In what concerns arterial stiffness, our study disclosed no difference between diabetics and controls. Moreover, Acetylcholine response can be correlated to arterial stiffness in diabetics, and further studies aiming at the evaluation of the micro and macrovascular reactivity should be performed with consumers of drugs which may be likely to affect the endothelial function.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A disfunção endotelial tem sido sugerida como evento precoce na patogênese das complicações vasculares do DM1. O presente estudo objetivou avaliar a função endotelial na microcirculação e rigidez arterial no diabetes tipo 1 comparando com controles não diabéticos e correlacionando com variáveis clínicas, demográficas e laboratoriais. Foram avaliados 57 pacientes com diabetes tipo 1 com idade de 32,5 (13-61) anos e duração de doença de 15 (1-48) anos e 53 controles através de fluxometria cutânea por laser-Doppler após iontoforese de Acetilcolina(ACh) (resposta endotélio dependente), hiperemia reativa pós oclusiva(HRPO) e a capacidade máxima de vasodilatação após hiperemia térmica. Já a resposta endotélio independente foi avaliada após iontoforese de Nitroprussiato de sódio (NPS). A rigidez arterial foi mensurada através da análise da onda de pulso digital com os índices de rigidez arterial e de reflexão. Os pacientes diabéticos foram submetidos à avaliação clínica e laboratorial (histórico de tabagismo, dose diária de insulina, duração do diabetes, uso de drogas que alteram a função endotelial como anti-hipertensivos e estatinas, níveis pressóricos, índice de massa corporal, excreção urinária de albumina, perfil lipídico, controle glicêmico e níveis de proteína C-reativa). O fluxo microvascular médio em repouso não foi diferente entre pacientes e controles , assim como a complacência arterial mensurada através do índice de rigidez arterial e do índice de reflexão. A resposta vascular a vasodilatação mediada pela ACh encontrou-se significantemente reduzida nos pacientes (p=0,002). No entanto, apesar da diferença verificada na área abaixo da curva de NPS em relação ao controle, a análise por medidas repetidas não apontou diferença entre os grupos em relação às doses entre os grupos (p=0,15). A vasodilatação cutânea máxima induzida pela hiperemia térmica foi maior entre os controles em comparação com os diabéticos &#61677;93,6(24,5-379-,9) e 56,6(31,5-204,5), respectivamente p=0,04&#61693;. Por outro lado, durante a HRPO, o aumento máximo no fluxo e a área abaixo da resposta hiperêmica não divergiram entre pacientes e controles, embora o tempo para alcançar o fluxo máximo tenha sido maior nos diabéticos do que nos controles(p=0,02). As principais variáveis correlacionadas com a microcirculação foram o ácido úrico, a hemoglobina glicada, a idade e a proteína C reativa, e com a rigidez arterial, foram a duração do Diabetes, a Pressão arterial diastólica e o HDL. Apesar da correlação entre o uso de drogas com propriedades hemorreológicas e a rigidez arterial, a exclusão dos pacientes usuários daqueles medicamentos não alterou os resultados obtidos. Concluímos que, na população de diabéticos tipo 1 estudada, a resposta vascular endotélio dependente, e a capacidade máxima de vasodilatação estão significativamente reduzidas. Não houve diferença entre diabéticos e controles quanto à rigidez arterial. Ademais, a vasodilatação microcirculatória mediada pela Acetilcolina pode ser correlacionada com a rigidez arterial em diabéticos. Estudos posteriores devem ser realizados no intuito de avaliar a influência exercida pelas drogas que alteram a função endotelial sobre a reatividade micro e macrovascular. / Endothelial dysfunction in patients with type 1 diabetes appears to be an early event in the genesis of vascular complications. The purpose of the present study is to assess endothelial function in the microcirculation and arterial stiffness, by comparing with non-diabetic controls, and correlating with clinical, demographic and laboratorial parameters. We evaluated 57 patients with type 1 diabetes aged 32.5 (13-61) years and with a disease duration of 15 (1-48)years, and 53 controls using laser Doppler flowmetry during low-current iontophoresis of acetylcholine (ACh) (endothelium dependent response), post occlusive reactive hyperemia(PORH) and maximum vasodilator function during thermal hyperemia. Endothelium-independent response was measured after iontophoresis of sodium nitroprusside (SNP).The peripheral pressure waveform was analyzed to assess the arterial stiffness. Diabetic patients underwent clinical and laboratory evaluation (smoking, disease duration, daily insulin dose, use of medications that could improve endothelial function such as antihypertensive drugs and statins, blood pressure, body mass index, urinary albumin excretion, lipid profile, glycemic control and C-reactive protein levels-CRP). Mean resting microvascular flux did not differ between control subjects and patients with type 1 diabetes, as well as arterial stiffness assessed through stiffness index and reflection index. Microvascular response to ACh was significantly reduced in patients (p=0,002). However, despite the reduction ofAUC NPS, the analysis with repeated measures disclosed no difference between the groups in relation to the doses (p=0,15). Maximal skin microvascular vasodilation induced by thermal hyperemia was found to be higher in the control group than among patients (&#61677;93,6(24,5-379-,9) e 56,6(31,5-204,5), respectively p=0,04). On the other hand, during PORH, maximal increase in flux and area under the curve of the hyperemic response did not differ between patients and controls, although the time frame to reach maximum flux and the time to half recovery after hyperemia was longer in patients than in controls (P=0.02) . Uric acid, hba1c, age and CRP were the most important contributing factors to the variation of microvascular reactivity, while disease duration, the diastolic arterial pressure and HDL cholesterol were independently associated to arterial stiffness. Despite the correlation between drugs with hemorheologycal properties and arterial stiffness, the exclusion of patients who were taking such substances did not affect the results. We conclude that in the studied population of type 1 diabetic patients, the endothelium-dependent vascular responses and maximal vasodilator capacity are significantly reduced. In what concerns arterial stiffness, our study disclosed no difference between diabetics and controls. Moreover, Acetylcholine response can be correlated to arterial stiffness in diabetics, and further studies aiming at the evaluation of the micro and macrovascular reactivity should be performed with consumers of drugs which may be likely to affect the endothelial function.