Thermal analysis of vascular reactivity

Cardiovascular disease (CVD) is the leading cause of death in the United States. Analysis of vascular reactivity (VR) in response to brachial artery occlusion is used to estimate arterial health and to determine the likelihood of future cardiovascular complications. Development of a sensitive technique to assess VR is fundamental to the field of preventive cardiology. The conventional technique to study VR is by monitoring arterial diameter changes during hyperemia following occlusion using ultrasound based methods. Such measurements require highly qualified technicians and expensive equipment; and are complicated by signal noise introduced by motion and posture among others. It is well known that tissue temperature changes are a direct response to variations in blood flow, and it has been observed in small clinical studies that variations in fingertip temperature during brachial artery occlusion and subsequent hyperemia is a simple surrogate for the measurement of vascular reactivity and endothelial dysfunction. Given the promising nature of thermal monitoring to study VR, this thesis focuses on the analysis of the underlying physics affecting fingertip temperature during vascular occlusion and subsequent hyperemia. I will quantify the contribution of hemodynamic, anatomical and environmental factors over digit temperature changes, which will serve to determine the sensitivity of the digital thermal monitoring (DTM) technique. I have quantified the effect of several contributing factors to fingertip temperature and DTM results. The aims of this thesis focus on: (1) creation of a mathematical model of heat transfer at baseline, during, and after a reactive hyperemia test; and (2) validation of the model and experimental analysis of thermal and flow parameters in healthy volunteers. The proposed project is an innovative study that intends to show and quantify the relationship between VR and digital thermal reactivity, translating mathematical models based on the physics of heat transfer and fluid mechanics to clinical application. The parametric studies performed with the zeroth order model served to separate the contribution of environment and blood flow over the temperature curves measured during brachial artery occlusion. The thermal models developed were able to reproduce the trend of the temperature response observed experimentally at the fingertip

Design of a thermal diffusion sensor for noninvasive assessment of skin surface perfusion and endothelial dysfunction

Thesis (M. Eng.)--Harvard-MIT Division of Health Sciences and Technology, 2008.Includes bibliographical references (p. 105-121).The skin microcirculation performs a range of vital functions, such as maintaining nutritional perfusion to the tissues and overall thermoregulation. Not only does impairment to the skin blood supply lead to tissue necrosis and other disease complications, increasing evidence shows that dysfunctional vasoreactivity in the skin microcirculation is associated with multiple disease states, including hypertension, diabetes mellitus, hypercholesterolemia, peripheral vascular disease, and coronary artery disease, and it is one of the earliest indicators of systemic endothelial dysfunction, the precursor to atherosclerotic disease. Endothelial dysfunction is functionally characterized by abnormal vasomotor response to either a pharmacological or flow-mediated stimulus and can be demonstrated in the skin by measuring reperfusion following a period of ischemia, a phenomenon known as post-occlusive reactive hyperemia (PORH). In my research, I have reviewed the literature regarding endothelial dysfunction and its association with a wide range of cardiovascular risk factors. I have also described the mechanisms thought to link endothelial function in the central vascular beds (i.e. coronary) to that of peripheral conduit vessels and the microcirculation. The knowledge thus gathered confirmed that the microcirculation of the skin is an appropriate site for endothelial function assessment. The ultimate goal of my thesis is to design a noninvasive sensor that is capable of obtaining a quantitative measure of skin perfusion, continuously and in real-time, using the principle of thermal diffusion in perfused tissue. I performed preliminary noninvasive endothelial function testing with a modified Thermal Diffusion Probe (TDP), which has been previously validated for absolute perfusion measurement in an invasive setting.(cont.) Based on an initial analysis, I have shown that thermal surface perfusion measurements are feasible and reflect the natural perfusion and temperature fluctuations intrinsic to skin tissue. I also established guidelines for determining quantitative parameters of reactivity from tests of PORH as well as temporal parameters of perfusion variations over time through a spectral analysis of resting blood flow. After establishing the necessary thermal boundary conditions for obtaining surface perfusion measurements, I embarked on a process of computer-assisted modeling and rapid prototyping of various design iterations on an insulated sensor housing, with subsequent fabrication of first generation noninvasive sensors. As a result of these initial sensor designs, specifications for the sensor housing were created to ensure that the appropriate thermal field would be established at the skin measurement site - an important step as it permits the most accurate determination of tissue thermal properties. Finally, I propose a candidate design for an ideal sensor capable of improving the reproducibility of noninvasive perfusion measurements on skin. The development of a noninvasive measure of endothelial dysfunction in the skin is of great value in the early identification of individuals at risk for atherosclerotic complications. Furthermore, the nature of such a technique would provide quantitative information on the presence of a disorder, the extent of dysfunction, and the effectiveness of treatment interventions.by Vivian V. Li.M.Eng

The application of infrared thermography in evaluation of patients at high risk for lower extremity peripheral arterial disease

ObjectiveWe investigated the usefulness of infrared thermography in evaluating patients at high risk for lower extremity peripheral arterial disease (PAD), including severity, functional capacity, and quality of life.MethodsA total of 51 patients (23 males; age 70 ± 9.8 years) were recruited. They completed three PAD-associated questionnaires, including walking impairment, vascular quality of life, and 7-day physical activity recall questionnaires before a 6-minute walking test (6MWT). Ankle-brachial index (ABI) and segmental pressure were analyzed for PAD diagnosis and stenotic level assessment. The cutaneous temperature at shin and sole were recorded by infrared thermography before and after the walk test. Detailed demographic information and medication list were obtained.ResultsTwenty-eight subjects had abnormal ABI (ABI <1), while PAD was diagnosed in 20. No subjects had non-compressible artery (ABI >1.3). Demographic profiles and clinical parameters in PAD and non-PAD patients were similar, except for age, smoking history, and hyperlipidemia. PAD patients walked shorter distances (356 ± 102 m vs 218 ± 92 m; P < .001). Claudication occurred in 14 patients, while seven failed in completing the 6MWT. The rest temperatures were similar in PAD and non-PAD patients. However, the post-exercise temperature dropped in the lower extremities with arterial stenosis, but was maintained or elevated slightly in the extremities with patent arteries (temperature changes at sole in PAD vs non-PAD patients: −1.25 vs −0.15°C; P < .001). The exercise-induced temperature changes at the sole were not only positively correlated with the 6MWD (Spearman correlation coefficient = 0.31, P = .03), but was also correlated with ABI (Spearman correlation coefficient = 0.48, P < .001) and 7-day physical activity recall scores (Spearman correlation coefficient = 0.30, P = .033).ConclusionBy detecting cutaneous temperature changes in the lower extremities, infrared thermography offers another non-invasive, contrast-free option in PAD evaluation and functional assessment

Medical Laser-Induced Thermotherapy - Models and Applications

Heat has long been utilised as a therapeutic tool in medicine. Laser-induced thermotherapy aims at achieving the local destruction of lesions, relying on the conversion of the light absorbed by the tissue into heat. In interstitial laser-induced thermotherapy, light is focused into thin optical fibres, which are placed deep into the tumour mass. The objective of this work was to increase the understanding of the physical and biological phenomena governing the response to laser-induced thermotherapy, with special reference to treatment of liver tumours and benign prostatic hyperplasia. Mathematical models were used to calculate the distribution of light absorption and the subsequent temperature distribution in laser-irradiated tissues. The models were used to investigate the influence on the temperature distribution of a number of different factors, such as the design of the laser probe, the number of fibres, the optical properties of the tissue, the duration of irradiation, blood perfusion and boundary conditions. New results concerning transurethral microwave thermotherapy were obtained by incorporating the distribution of absorbed microwaves into the model. Prototypes of new laser applicators for anatomically correct treatment of benign prostatic hyperplasia were developed and tested ex vivo. Experimental work on liver tumours pointed to the importance of eliminating the blood flow in the liver during treatment to reduce convective heat loss. In addition, it was shown that hepatic inflow occlusion during treatment increased the thermal sensitivity of tumour tissue. The dynamic influence of interstitial laser thermotherapy on liver perfusion was investigated using interstitial laser Doppler flowmetry. Vessel damage after the combined treatment of laser-induced heat treatment and photodynamic therapy was studied

Velocity profiles and turbulence in the aorta : a study by hot-film anemometry

Imperial Users onl

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

An Experimental and Theoretical Analysis of Nitric Oxide in the Microcirculation

Nitric Oxide (NO) is produced in the vascular endothelium where it then diffuses to the adjacent smooth muscle cells (SMC) activating agents known to regulate vascular tone. The close proximity of the site of NO production to the red blood cells (RBC) and its known fast consumption by hemoglobin, suggests that the blood will scavenge most of the NO produced. Therefore, it is unclear how NO is able to play its role in accomplishing vasodilation. Investigation of NO production and consumption rates will allow insight into this paradox. DAF-FM is a sensitive NO fluorescence probe widely used for qualitative assessment of cellular NO production. With the aid of a mathematical model of NO/DAF-FM reaction kinetics, experimental studies were conducted to calibrate the fluorescence signal showing that the slope of fluorescent intensity is proportional to [NO]2 and exhibits a saturation dependence on [DAF-FM]. In addition, experimental data exhibited a Km dependence on [NO]. This finding was incorporated into the model elucidating NO2 as the possible activating agent of DAF-FM. A calibration procedure was formed and applied to agonist stimulated cells, providing an estimated NO release rate of 0.418 ± 0.18 pmol/cm2s. To assess NO consumption by RBCs, measurements of the rate of NO consumption in a gas stream flowing on top of an RBC solution of specified Hematocrit (Hct) was performed. The consumption rate constant (kbl)in porcine RBCs at 25oC and 45% Hct was estimated to be 3500 + 700 s-1. kbl is highly dependent on Hct and can reach up to 9900 + 4000 s-1 for 60% Hct. The nonlinear dependence of kbl on Hct suggests a predominant role for extracellular diffusion in limiting NO uptake. Further simulations showed a linear relationship between varying NO production rates and NO availability in the SMCs utilizing the estimated NO consumption rate. The corresponding SMC [NO] level for the average NO production rate estimated was approximately 15.1 nM. With the aid of experimental and theoretical methods we were able to examine the NO paradox and exhibit that endothelial derived NO is able to escape scavenging by RBCs to diffuse to the SMCs

Electrochemically Modulated Generation/Delivery of Nitric Oxide (NO) from Nitrite for Biomedical Applications.

In this dissertation research, the development of a new electrochemically modulated NO generation/delivery approach was examined. Further, the potential application of this approach in devising advanced thromboresistant/bactericidal intravascular catheters and a new NO inhalation therapy system was explored. Nitric oxide can be generated from nitrite via two electrochemical approaches: 1) using a Cu0 wire and an applied anodic/cathodic potential pulse sequence to electrochemically reduce nitrite to NO (Chapter 2); and 2) using Pt/Au or other working electrodes and a soluble Cu(II)-ligand complex as mediator to reduce nitrite to NO (Chapter 3). The temporal pattern of NO generation can be precisely modulated in the latter system by the applied potential or current. This electrochemical NO release system was first incorporated within intravascular catheters, which exhibited much reduced clotting (~85 %) in vivo and significantly less (>99.9%) microbial biofilm in vitro compared to non-NO release control devices. Further, this NO release concept was combined with an amperometric oxygen sensor (PO2 sensor) within a dual-lumen catheter configuration (Chapter 4) for intravascular continuous monitoring of PO2 levels. Electrochemical NO release was fully compatible with PO2 sensing and yielded more accurate PO2 measurements (vs. controls) when implanted in arteries of pigs for 20 h. In Chapter 5, the electrochemical NO release catheters were used for controlled delivery of NO to elucidate the dosage effect of NO on mature P. aeruginosa biofilm. Fluxes of NO >0.5 × 10^-10 mol min-1 cm-2 showed 99% killing of the biofilm in 3 h, and such an effect was in synergy with added gentamicin. In Chapter 6, the new electrochemical NO delivery method was employed for developing a gas phase NO inhalation (INO) system. Relatively pure gas phase NO in the range of 1–150 ppmv can be created by this system. Finally, the partitioning and diffusion properties of NO within several biomedical polymers was examined (Chapter 7), with silicone rubber exhibiting the optimal transport of NO. Overall, electrochemical delivery of NO provides both a tool for fundamental biological studies, as well as a means to improve the biocompatibility of medical devices.PhDChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/120688/1/renhang_1.pd