Magnetic Resonance Imaging (MRI) is a widely used, non-invasive imaging technique that provides a means to reveal structural and functional information of different body tissues in detail. Susceptibility Weighted Imaging (SWI) is a field in MRI that utilizes the information from the magnetic susceptibility property of different tissues using the gradient echo phase information. Although longer echo times (TEs) have been widely used in applications involving SWI, there are a few problems related with the long TE data, such as the strong blooming effect and phase aliasing even at macroscopic levels. In this thesis, the use of very short TEs is proposed to study susceptibility mapping. The short TEs can be used to study structures with susceptibilities an order of magnitude larger (such as air and bones in and around the brain sinuses, skull and teeth) than those within soft tissue. Using a new iterative susceptibility mapping technique that we recently developed, it becomes possible to map the geometry of such structures, which to date has proven difficult due to the lack of water content (for sinuses) or due to very short T2* (for bones). The method of phase replacement inside the sinuses proposed in this thesis provides more accurate phase information for the inversion than assuming zero or some arbitrary constant inside these structures. The first and second iterations were responsible for most of the changes in mapping out the susceptibility values. The mean susceptibility value in the sphenoid sinus is calculated as +9.3 ± 1.1ppm, close to the expected value of +9.4ppm for air. The reconstruction of the teeth in the in-vivo data provides a mean Δχ(teeth-tissue)=–3.3ppm, thanks to the preserved phase inside the jaw. The mean susceptibility inside a relatively homogeneous region of the skull bone was measured to be Δχ(bone-tissue)=–2.1ppm. Finally, these susceptibilities can be used to help remove the unwanted background fields prior to applying either SHARP or HPF. In addition, the effects of the background field gradient on flow compensation are studied. Due to the presence of these background gradients, an unwanted phase term is induced by the blood flow inside the vessels. Using a 3D numerical model and in vivo data, the background gradients were estimated to be as large as 1.5mT/m close to the air-tissue interfaces and 0.7mT/m inside the brain (leading to a potential signal loss of up to 15%). The quantitative susceptibility mapping (QSM) results were improved in the entire image after removing the confounding arterial phase thanks to the reduced ringing artifacts. Lastly, a novel approach to improve the susceptibility mapping results was introduced and utilized to monitor the changes in venous oxygen saturation levels as well as the changes in oxygen extraction fraction instigated by the vasodynamic agents, caffeine and acetazolamide. The internal streaking artifacts in the susceptibility maps were reduced by giving an initial susceptibility value uniformly to the structure-of-interest, based on the a priori information. For veins, the iterative results, when the initial value of 0.45 ppm was used, were the best in terms of the highest accuracy in the mean susceptibility value (0.453 ppm) and the lowest standard deviation (0.013 ppm). Using this technique, the venous oxygen saturation levels (inside the internal cerebral veins (ICVs)) for normal physiological conditions, post-caffeine and post-Diamox for the first volunteer were calculated as (mean ± standard deviation): Y_Normal = 69.1 ± 3.3 %, Y_Caffeine = 60.5 ± 2.8 % and Y_Diamox = 79.1 ± 4.0%. For the caffeine challenge, the percentage change in oxygen extraction fraction (OEF) for pre and post caffeine results was calculated as +27.0 ± 3.8%; and for the Diamox challenge, the percentage change in OEF was calculated as −32.6 ± 2.1 % for the ICVs. These vascular effects of Diamox and caffeine were large enough to be easily measured with susceptibility mapping and can serve as a sensitive biomarker for measuring reductions in cerebro-vascular reserve through abnormal vascular response, an increase in oxygen consumption during reperfusion hyperoxia or locally varying oxygen saturation levels in regions surrounding damaged tissue. In conclusion, our new approach to QSM offers a means to monitor venous oxygen saturation reasonably accurately and may provide a new means to study neurovascular diseases where there are changes in perfusion that affect the oxygen extraction fraction. / Thesis / Doctor of Philosophy (PhD) / Magnetic Resonance Imaging (MRI) is a widely used, non-invasive imaging technique that provides a means to reveal structural and functional information of different body tissues in detail. Susceptibility Weighted Imaging (SWI) is a field in MRI that utilizes the information from the magnetic susceptibility property of different tissues using the gradient echo phase information. Firstly, we demonstrate that using our phase replacement technique, it becomes possible to map the geometry of structures with almost no MR signal, which to date has proven difficult due to the lack of water content (for sinuses) or due to very short T2* (for bones). Secondly, the effects of the background field gradient on flow compensation were studied. Due to the presence of these background gradients, an unwanted phase term is induced by the blood flow inside the vessels. And, lastly, we present our new approach utilizing SWI data, offering a means to monitor venous oxygen saturation reasonably accurately and, potentially, a new means to study neurovascular diseases where there are changes in perfusion that affect the oxygen extraction fraction.

Frequency Domain Diffuse Optical Spectroscopy (FD-DOS) is an emerging optical technique that uses near infrared light to probe the hemodynamics of biological tissue. Compared to more common Continuous Wave (CW) methods, FD-DOS uses light that is temporally modulated on the order of MHz to quantify the absorption and scattering of tissue. FD-DOS can also be used to obtain absolute concentration of tissue chromophores such as oxy- and deoxy-hemoglobin, which allow for quantitative measurements of tissue hemodynamics. This dissertation focuses on the evolution of our lab’s custom digital FD-DOS as a platform for taking optical measurement of biological tissue for respiratory and cardiovascular applications. Several important instrumentation improvements will be reviewed that have enhanced the performance of the system while making it more portable and clinic ready. Two translational applications will be described in detail: 1) the use of high-speed FD-DOS for the non-invasive extraction of venous oxygen saturation (SvO2) and 2) the use of FD-DOS to monitor the hemodynamics of the sternocleidomastoid (SCM) muscle towards the non-invasive monitoring of patients on mechanical ventilation. The custom FD-DOS system parameters were adjusted for each application, with a focus on high speed to extract the cardiac signal for the SvO2 project, and a focus on high SNR to measure the highly absorbing SCM. Measurements on healthy volunteers and rabbits were used to assess the feasibility of using FD-DOS for these applications. Finally, preliminary work was conducted to characterize a miniature FD-DOS source and detector with the goal of moving towards a wearable version of FD-DOS. / 2022-05-15T00:00:00Z

<p>Systemic infection, major surgery, trauma and many other causes can lead to impaired organ function. Compensated shock is not detected by global hemodynamic and oxygen measurements, as they take no account for regional variations. Focus has therefore gradually turned from looking at systemic changes to selective investigations of regional blood flow and ischemia. This thesis presents a series of experiments evaluating new application and validation of various monitoring techniques.</p><p>An experimental porcine model with anesthetized and invasively monitored animals was used. The circulatory interventions included endotoxin infusion (septic shock), aortic constriction and selective clamping of splanchnic arteries. The aim was to compare air with saline tonometry, to validate the intraperitoneal use of tonometry and to reexamine the use of endoluminal reflectance pulse oxymetry. To investigate the relative contributions of regional blood flow and detection of ischemia, measurements of hepatic venous oxygen saturation (ShvO₂), lactate concentrations and PCO₂ gap were used.</p><p>Our findings support the use of air instead of saline as the preferred technique for tonometric measurements. With the intraperitoneal application of tonometry we gain more information on regional aspects of the splanchnic circulation, and it appears to be a reliable monitoring option for early detection of ischemia in the small intestine. Measurements of ShvO₂will give an overall reflection of the intestinal circulation. The sigmoid colonic pulse oximetry showed a non-linear response in relation to regional blood flow, and will therefore not be able to detect gradual changes in oxygen saturation. Determination of the regional to endtidal PCO₂ gap might prove valuable for monitoring of the intestinal circulation.</p><p>Because of sophisticated interactions between portal and hepatic arterial blood flow and hepatic compensation for regional ischemia, a combination of monitoring techniques might be needed. The results of this study will hopefully encourage clinical evaluation of intraperitoneal tonometry and endtidal PCO₂ gap recordings for non-invasive, semi-continuous, trend monitoring of the splanchnic circulation.</p>

Systemic infection, major surgery, trauma and many other causes can lead to impaired organ function. Compensated shock is not detected by global hemodynamic and oxygen measurements, as they take no account for regional variations. Focus has therefore gradually turned from looking at systemic changes to selective investigations of regional blood flow and ischemia. This thesis presents a series of experiments evaluating new application and validation of various monitoring techniques. An experimental porcine model with anesthetized and invasively monitored animals was used. The circulatory interventions included endotoxin infusion (septic shock), aortic constriction and selective clamping of splanchnic arteries. The aim was to compare air with saline tonometry, to validate the intraperitoneal use of tonometry and to reexamine the use of endoluminal reflectance pulse oxymetry. To investigate the relative contributions of regional blood flow and detection of ischemia, measurements of hepatic venous oxygen saturation (ShvO2), lactate concentrations and PCO2 gap were used. Our findings support the use of air instead of saline as the preferred technique for tonometric measurements. With the intraperitoneal application of tonometry we gain more information on regional aspects of the splanchnic circulation, and it appears to be a reliable monitoring option for early detection of ischemia in the small intestine. Measurements of ShvO2 will give an overall reflection of the intestinal circulation. The sigmoid colonic pulse oximetry showed a non-linear response in relation to regional blood flow, and will therefore not be able to detect gradual changes in oxygen saturation. Determination of the regional to endtidal PCO2 gap might prove valuable for monitoring of the intestinal circulation. Because of sophisticated interactions between portal and hepatic arterial blood flow and hepatic compensation for regional ischemia, a combination of monitoring techniques might be needed. The results of this study will hopefully encourage clinical evaluation of intraperitoneal tonometry and endtidal PCO2 gap recordings for non-invasive, semi-continuous, trend monitoring of the splanchnic circulation.