Nasopharyngeal method for selective brain cooling and development of a time-resolved near-infrared technique to monitor brain temperature and oxidation status during hypothermia

Mild hypothermia at 32-35oC (HT) has been shown to be neuroprotective for neurological emergencies following severe head trauma, cardiac arrest and neonatal asphyxia. However, HT has not been widely deployed in clinical settings because: firstly, cooling the whole body below 33-34°C can induce severe complications; therefore, applying HT selectively to the brain could minimize adverse effects by maintaining core body temperature at normal level. Secondly, development of an effective and easy to implement selective brain cooling (SBC) technique, which can quickly induce brain hypothermia while avoiding complications from whole body cooling, remains a challenge. In this thesis, we studied the feasibility and efficiency of selective brain cooling (SBC) through nasopharyngeal cooling. To control the cooling and rewarming rate and because core body temperature is different from brain temperature, we also developed a non-invasive technique based on time-resolved near infrared spectroscopy (TR-NIRS) to measure local brain temperature. In normal brain, cerebral blood flow (CBF) and energy metabolism as reflected by the cerebral metabolic rate of oxygen (CMRO2) is tightly coupled leading to an oxygen extraction efficiency (OEF) of around ~33%. A decoupling of the two as in ischemia signifies oxidative stress and would lead to an increase in OEF beyond the normal value of ~33%. The final goal of this thesis is to evaluate TR-NIRS methods for measurements of CBF and CMRO2 to monitor for oxidative metabolism in the brain with and without HT treatment. Chapter 2 presents investigations on the feasibility and efficiency of the nasopharyngeal SBC by blowing room temperature or humidified cooled air into the nostrils. Effective brain cooling at a median cooling rate of 5.6 ± 1.1°C/hour compared to whole body cooling rate of 3.2 ± 0.7 was demonstrated with the nasopharyngeal cooling method. Chapter 3 describes TR-NIRS experiments performed to measure brain temperature non-invasively based on the temperature-dependence of the water absorption peaks at ~740 and 840nm. The TR-NIRS method was able to measure brain temperature with a mean difference of 0.5 ± 1.6°C (R2 = 0.66) between the TR-NIRS and thermometer measurements. Chapter 4 describes the TR-NIR technique developed to measure CBF and CMRO2 in a normoxia animal model under different anesthetics at different brain temperatures achieved by whole-body cooling. Both CBF and CMRO2 decreased with decreasing brain temperature but the ratio CMRO2:CBF (OEF) remained unchanged around the normal value of ~33%. These results demonstrate that TR-NIR can be used to monitor the oxidative status of the brain in neurological emergencies and its response to HT treatment. In summary, this thesis has established a convenient method for selective brain cooling without decreasing whole body temperature to levels when adverse effects could be triggered. TR-NIRS methods are also developed for monitoring local brain temperature to guide SBC treatment and for monitoring the oxidation status of the brain as treatment progresses

Microcirculatory and Mitochondrial PO2 in different (Patho-)Physiological states of the rat heart

Handling and availability issues of oxygen are relevant processes fueling evolution of several diseases. Measuring oxygen in organs, at cellular and subcellular level bears several challenges. Earlier our group had developed dual-wavelength phosphorimeter allowing measurements of microcirculatory PO2 at two depths. Then, adaptation of this technique made the measurement of mitochondrial pO2 possible. The next logic step accomplished in this thesis was to combine both techniques. The aim of the thesis was therefore to further develop and characterize this phosphorimetric method of near-simultaneous measurements of microcirculatory and mitochondrial oxygenation in the heart in vivo. Then in two animal models, namely endotoxemia and right ventricular pressure overload, we measured the oxygenation level in the microcirculation and mitochondria and investigated the changes induced by therapeutic interventions. We hypothesized that in sepsis hypoxia would be found in non-resuscitated animals but no oxygen shortage would be found with supportive therapy indicating oxygen management issues arising from mitochondrial dysfunction. In pressure overload induced right heart failure we expected a switch increased anaerobic glycolysis without occurrence of hypoxia.<br/

A Clinician's Contribution to Biomedical Engineering in Experimental Echocardiography

The research of this thesis has been focused on the biomedical engineering aspects of new techniques of echocardiography. In close collaboration with the engineers of the Experimental Echocardiography Department of the Thoraxcentre, Erasmus University, Rotterdam, new methods to measure coronary blood flow and arterial wall elasticity with intravascular ultrasound (IVUS) have been developed. We have also investigated the clinical application of these measurements and have tried to improve traditional techniques based on intracoronary Doppler wires. In another field, we have developed a method to determine the radiation dose delivered in the wall of coronary arteries treated with brachytherapy. in collaboration with the Emory University, Atlanta, GA. This method utilizes 3-dimensional IVUS reconstruction combined with radiotherapy treatment planning. Finally, the tools developed for the recording of the signals of intracoronary Doppler wires have been adapted, during a stay at the Cleveland Clinic Foundation, OK for the study of left ventricular mechanics and the compliance of the large arteries. This has been achieved by simultaneous acquisition of non-invasive pressure (with tonometry) and flow (with transthoracic Doppler echocardiography) signals. The fruits of an old and close collaboration with the Institute Biomedical Technology of the Ghent University can also be found in different chapters. This work is subdivided in five major parts, and a detailed introductory chapter precedes each one

Intracoronary ultrasound

Knowledge of the characteristics of the atherosclerotic plaque (eccentricity, composition, effect of initial dilatation or ablation) and of the flow modifications induced by a coronary stenosis would establish more precisely the severity of the lesion under evaluation, improve the planning and guidance of therapeutic interventions, and facilitate the detection of subsequent complications. The miniaturization of the ultrasound catheters a11d the de

Intravascular Ultrasound

Intravascular ultrasound (IVUS) is a cardiovascular imaging technology using a specially designed catheter with a miniaturized ultrasound probe for the assessment of vascular anatomy with detailed visualization of arterial layers. Over the past two decades, this technology has developed into an indispensable tool for research and clinical practice in cardiovascular medicine, offering the opportunity to gather diagnostic information about the process of atherosclerosis in vivo, and to directly observe the effects of various interventions on the plaque and arterial wall. This book aims to give a comprehensive overview of this rapidly evolving technique from basic principles and instrumentation to research and clinical applications with future perspectives

Optical coherence tomography for the assessment of coronary atherosclerosis and vessel response after stent implantation

Optical Coherence Tomography (OCT) is a light-based imaging modality that can provide in vivo high-resolution images of the coronary artery with a level of resolution (axial 10-20 µm) ten times higher than intravascular ultrasound. The technique, uses low-coherent near infrarred light to create high-resolution cross sectional images of the vessel. The technology refinement achieved in the last years has made this imaging modality less procedurally demanding opening its possibilities for clinical use. The present thesis provides im