PHD, Kent State University, 2013, College of Education, Health and Human Services / School of Health Sciences

Previous research suggests that physical activity may result in to decreases in arterial saturation (SaO2) and cerebral blood flow when exposed to a low oxygen environment between aerobically fit and unfit males. Purpose: The purpose of this study was to determine differences in SaO2, cerebral blood flow, minute ventilation (VE), and blood lactate between fit and unfit young males during exercise in hypoxia compared to normoxia. Methods: Apparently healthy college age males took part in two trials consisting of normobaric normoxia and normobaric hypoxia (12% oxygen). Fit (n = 3; VO2max = 51.5 ml ¿ kg-1 ¿ min-1 ± 3.1) and Unfit (n = 3; VO2max = 34.4 ml ¿ kg-1 ¿ min-1 ± 5.6) males cycled at 50% of their altitude adjusted VO2max (-26% of normoxia VO2max) for one hour after a two-hour baseline. Results: SaO2, cerebral blood flow, and RER were significantly decreased during hypoxia in all subjects (P < 0.05), but did not differ between groups. An interaction showed that Fit subjects had a higher SaO2 during exercise in hypoxia (P < 0.05). VE and lactate was greater during hypoxia (P < 0.05). The Fit group demonstrated a higher VE during exercise in hypoxia (P < 0.05). No differences in blood lactate were found between the two groups. Conclusion: The data suggests that when exposed to hypoxia aerobically unfit males may demonstrate decrements in oxygen utilization which may lead to decreases in physical activity and/or performance.

Committee: Ellen Glickman Ph.D. (Committee Chair); Jacob Barkley Ph.D. (Committee Member); John Gunstad Ph.D (Committee Member) Subjects: Environmental Health; Health; Physiology

Doctor of Philosophy (PhD), Wright State University, 2023, Engineering PhD

Blood flow dynamics plays a critical role in maintaining tissue health, as it delivers nutrients and oxygen while removing waste products. It is especially important when there is a disruption in cerebral autoregulation due to trauma, which can induce ischemia or hyperemia and can lead to secondary brain injury. Thus, there is a need for noninvasive techniques that can allow continuous monitoring of blood flow during intervention. Optical techniques have become increasingly practical for measuring blood flow due to their non-invasive, continuous, and relatively lower-cost nature. This research focused on developing a low-cost, scalable optical technique for measuring blood flow by implementing speckle contrast optical spectroscopy using a fiber-camera-based approach. This technique is particularly well-suited for measuring blood flow in deep tissues, such as the brain, which is challenging to access using traditional optical methods. A two-channel continuous wave speckle contrast optical spectroscopy device was developed, and the device was rigorously tested using phantoms. Then, it is applied to monitor blood flow changes in the brain following traumatic brain injury (TBI) in mice. The results indicate that trauma-induced significant blood flow decreases consistent with the recent literature. Overall, this approach provides noninvasive continuous measurements of blood flow in preclinical models such as traumatic brain injury.

Committee: Ulas Sunar Ph.D. (Advisor); Tarun Goswami Ph.D. (Committee Member); Keiichiro Susuki Ph.D. (Committee Member); Robert Lober M.D., Ph.D. (Committee Member) Subjects: Biomedical Engineering; Biomedical Research; Biophysics; Engineering; Optics

PhD, University of Cincinnati, 2022, Pharmacy: Pharmaceutical Sciences

Traumatic brain injury (TBI) is a significant cause of death and disability with an estimated 176 TBI-related deaths occurring each day within the United States alone. While everyone is exposed to factors that could lead to a TBI, certain groups of individuals are at a higher risk for sustaining neurotrauma than others. The technological evolution of modern warfare has led to the increased use of explosive devices. Consequently, military personnel are experiencing more TBI related injuries with an estimated 20% of all military personnel suffering at least one TBI during their deployment. TBI leads to long term complications including depression, deficits in memory and learning, and increased risk for suicide and suicidal ideation. The lack of effective preventative measures to prevent TBI significantly contributes to the high rates of injury. While the causes of TBI are situational, the majority of TBIs result from the body experiencing deleterious acceleration/deceleration forces. These forces result in a dissipative transfer of energy between the brain and the skull resulting in significant strain and shear stress on the brain tissue. Despite the common misconception that helmets can protect against TBI, they are unable to effectively mitigate energy transmission and leave wearers susceptible to head injury. A small quantifiable volume dubbed the compensatory reserve volume (CRV) permits energy transmission to brain tissue during acceleration/deceleration events. Recent work has found that increases in cerebral blood flow (CBF) are able to exhaust the CRV and reduce the absorption of energy and damage to the brain resulting from acceleration/deceleration forces. The most powerful biologic determinant of CBF and therefore the CRV is the concentration of inspired Carbon Dioxide (CO2). We therefore hypothesized that experimental hypercapnia (i.e. increased inspired concentration of CO2) may prevent and mitigate the actions of acceleration/deceleration-induce (open full item for complete abstract)

Committee: Matthew Robson Ph.D. (Committee Member); Gary Gudelsky Ph.D. (Committee Member); Eric Wohleb (Committee Member); Timothy Phoenix Ph.D. (Committee Member); Jennifer McGuire Ph.D. (Committee Member) Subjects: Pharmaceuticals

Doctor of Philosophy (PhD), Wright State University, 2021, Engineering PhD

Measuring cerebral blood flow (CBF) is a crucial element in monitoring a vast variety of human brain disorders. Current imaging modalities used for measuring CBF has various limitations that restricts its usefulness especially in the neuroscience intensive care unit (NSICU). Here, the use of Time-gated DCS (TG-DCS) which has significant advantages compared to its predecessor, CW-DCS, was proposed as the solution. However, this technology is still in its infancy and its clinical capability has yet to be established. To show the feasibility of deploying TG-DCS in NSICU settings, the time-domain analytical model for TG-DCS was expanded for multi-layered cases. Next, CW-DCS was validated in humans and in NSICU settings on patients suffering from Traumatic Brain Injury (TBI). A prototype 1064nm TG-DCS system was built and validated on several in-vivo experiments. Finally, the feasibility of the system was shown by deploying it in NSICU settings for measuring CBF in TBI patients. Lastly, deep learning was used to show the feasibility of obtaining real-time results.

Committee: Ulas Sunar Ph.D. (Advisor); Sherif Elbasiouny Ph.D. (Committee Member); Robert Lober M.D., Ph.D. (Committee Member); Brandon Foreman M.D. (Committee Member); Jonathan Lovell Ph.D. (Committee Member) Subjects: Artificial Intelligence; Biomedical Engineering; Biomedical Research; Biophysics; Medical Imaging; Neurosciences; Optics

Doctor of Philosophy, Case Western Reserve University, 2017, Applied Mathematics

The increased cerebral metabolic rate following neural activity triggers a rapid increase in cerebral blood flow (CBF), a phenomenon that is at the base of several functional imaging modalities, e.g., optical diffusion tomography and BOLD-fMRI. While the connection between the brain activity and increased CBF has been demonstrated, the details of the neurovascular coupling remain unclear. Mathematical models of cerebral hemodynamics assume a ballooning of the vessels to accommodate the additional blood, however, many details of these models remain to be explained, and several of the key parameters are unknown. To model mathematically the vascular system's response to neural activation by increasing vascular compliance, an auxiliary function, a vasodilatory stimulus function, is introduced, however, there is no quantitative way to observe or measure it. Implicitly, estimating this function from blood flow data gives a way to infer on the compliance. Addressing these issues, we set up a series of inverse problems to estimate parametric and nonparametric vasodilatory stimuli from observations of CBF, in which we consider multiple vascular compartmental locations of the vasodilation. The less restrictive approach of the estimation, where we assume a nonparametric model of the stimulus, requires either regularization or use of prior information. We propose here an approach based on Bayesian hierarchical models, utilizing qualitative a priori knowledge. Moreover, to address the computational issues arising in the estimation process, we use Krylov subspace iterative methods and present a novel, statistically motivated stopping criterion for the CGLS iterations. Finally, we introduce a statistical modeling error framework to account for the uncertainties in the poorly known model parameters. Computed examples illustrate the effectiveness of the proposed approaches and demonstrate the need for uncertainty quantification techniques.

Committee: Daniela Calvetti PhD (Advisor); Erkki Somersalo PhD (Advisor); David Gurarie PhD (Committee Member); Joseph LaManna PhD (Committee Member) Subjects: Applied Mathematics

PHD, Kent State University, 2015, College of Arts and Sciences / Department of Psychological Sciences

Cognitive impairment is common in heart failure (HF) and proposed to stem from reduced cerebral blood flow subsequent to the effects of cardiac dysfunction and comorbid medical conditions. Obesity is found in up to 40% of HF patients and is a known contributor to cognitive dysfunction and decreased cerebral blood flow. However, no study has simultaneously examined whether increases in body mass index (BMI) over time corresponds to accelerated cerebral hypoperfusion and cognitive decline. The current study sought to determine whether changes in BMI predicted cerebral perfusion and cognitive function over a 12-month period in HF patients. 122 HF patients were administered a cognitive battery that assessed global cognition, attention/executive function, memory, and language. Participants also completed transcranial Doppler ultrasonography to quantify cerebral blood flow (CBF). These procedures were repeated at 3- and 12-months. At baseline, 45.9% of the sample had a BMI consistent with obesity, which remained stable over time. Latent growth curve modeling (LGM) showed good model fit for improvements in global cognition and memory and declines in CBF over time. However, change in both BMI and CBF over time did not emerge as predictors of these trajectories. Cross-sectional analyses at each time point also showed no association between BMI with cognitive function and CBF. Follow-up analyses revealed a trend between better baseline treatment adherence and improved global cognitive function. In sum, BMI was not predictive of cognitive decline or reduced CBF over a 12-month period. In contrast, the observed cognitive improvements might be related to better treatment adherence. CBF also declined over time and prospective studies with extended follow-ups (e.g., 2-5 years) should clarify whether continued reductions of cerebral blood flow leads to cognitive worsening.

Committee: John Gunstad Ph.D. (Committee Chair); Spitznagel Mary Beth Ph.D. (Committee Member); Ciesla Jeffrey Ph.D. (Committee Member); Merriman William Ph.D. (Committee Member); Glickman Ellen Ph.D. (Committee Member); Barkley Jacob Ph.D. (Committee Member) Subjects: Aging; Medicine; Neurosciences; Psychology

Master of Science in Engineering (MSEgr), Wright State University, 2011, Biomedical Engineering

A brain stimulation technology called transcranial direct current stimulation (tDCS) may potentially mitigate the vigilance decrement. To practically use such technology, however, a model is necessary that indicates vigilance performance, both when stimulation is being applied and not applied. To address this issue, the author developed models capable of predicting vigilance performance in real and control stimulation conditions using previous tDCS-study data. The “all possible combinations” regression method produced over 200 models, later screened to 10. The model with the best average %error (11.49 ± 0.10) used left hemispheric cerebral blood flow velocity (CBFVL) as its sole input term-accounting for 95.7% of the performance variability (linear best-fit slope of 0.8585). When applied to the control stimulation condition, the model had an average %error of 16.76 ± 0.17 and linear best-fit slope of 0.9278. Such results suggest that CBFVL may be useful as a vigilance performance metric during tDCS applications.

Committee: Jennie Gallimore PhD (Advisor); Andy McKinley PhD (Committee Member); David Reynolds PhD (Committee Member) Subjects: Biomedical Engineering; Psychology

PhD, University of Cincinnati, 2008, Arts and Sciences : Psychology

Driver stress and fatigue are common problems that may impact safety. This study focuses especially on the threat to safety posed by driving in monotonous environments which elicit both subjective tiredness and performance impairment (Thiffault & Bergeron, 2003). It is important to distinguish between states of stress and fatigue, and traits that may predispose the driver to stress. Subjective stress and fatigue state responses can be assessed using the Dundee Stress State Questionnaire (DSSQ: Matthews, Campbell, Desmond, Huggins, Falconer, & Lucy, 1999), which evaluates stress states and arousal on the dimensions of Task Engagement, Distress, and Worry. The driver's general proneness towards stress may be assessed using the Driving Stress Inventory (DSI: Matthews, Desmond, Joyner, & Carcary, 1997). States of fatigue may also be measured using cerebral blood flow velocity (CBFV), assessed by transcranial Doppler sonography (TCD). Previous research in this laboratory has shown that the temporal decrement in vigilance performance is accompanied by declining CBFV and that CBFV responses to demanding tasks predict subsequent vigilance (Reinerman et al., 2007). The aim for this study was to investigate whether the utility of CBFV as a diagnostic index of stress and fatigue generalized from traditional vigilance paradigms to the task of driving. Consistent with previous research, driver performance deteriorated over time and the drive elicited increased distress and loss of task engagement. Additionally, CBFV decreased with time on task and the DSI fatigue proneness scale predicted lower task engagement during driving. On the whole, results of the present study offer support to the supposition that CBFV has some potential as a valid diagnostic index to predict fatigue while driving but further research is needed in this area.

Committee: Gerald Matthews Ph.D. (Committee Chair); Joel Warm Ph.D. (Committee Member); Giao Tran Ph.D. (Committee Member) Subjects: Psychology

PhD, University of Cincinnati, 2008, Arts and Sciences : Psychology

Vigilance or sustained attention is a critical aspect of many jobs including air-traffic control, medical screening/monitoring, and detection of illicit radioactive material at seaports and border crossings. An extensive review by Reinerman (2006) concluded that traditional approaches to personnel selection encompassing sensory acuity, aptitude, sex, age, and personality measures for tasks requiring sustained attention have been ineffective. The present study utilized the methodology from Reinerman et al. (2006), which attacked the selection issue using responses to a brief 10-min screening battery involving high workload tracking, verbal working-memory, and line discrimination tasks to predict performance on a subsequent sensory vigilance task. Two predictors of interest were cerebral blood flow velocity, measured via transcranial Doppler ultrasonography (Warm and Parasuraman, 2007) and subjective state, as indexed by the Dundee Stress State Questionnaire (Matthews et al; 2002). The present vigilance task was a letter transformation working-memory task and was composed of four consecutive 9-min periods. Such cognitive vigilance tasks require different information-processing components and responses than those of sensory tasks. The aim for the present study was to generalize the findings of Reinerman et al. (2006) to that of cognitive vigilance. Multiple regression (R = .577) indicated that higher levels of CBFV in the left and right hemispheres and higher post-battery task engagement scores on the DSSQ during performance of the screening battery predicted perceptual sensitivity (A') during the final period of watch when performance deficiencies are most likely to occur. Predictions from a correlation of this magnitude, which accounts for 28.1 percent of the variance when adjusted for shrinkage, can lead to an increase in job success rate of 40 to 60 percent (Rosenthal and Rubin, 1982). These findings were interpreted theoretically in light of a resource-workload mo (open full item for complete abstract)

Committee: Joel Warm PhD (Committee Chair); Matthews Gerald PhD (Committee Co-Chair); Stutz Robert PhD (Committee Member) Subjects: Psychology

MA, University of Cincinnati, 2007, Arts and Sciences : Psychology

Vigilance or sustained attention is a critical aspect of many jobs including air-traffic control, airport security, industrial quality control, and medical screening/monitoring. Traditional approaches to personnel selection for tasks requiring sustained attention have focused on sensory acuity, aptitude, sex, age, and personality measures. However these approaches have been ineffective. The present study attacked the selection issue in an innovative manner by using responses to a brief 10-min screening battery involving high workload tracking, verbal working memory, and line discrimination tasks to predict performance on a subsequent vigilance task. The latter simulated an air-traffic control task and was composed of four consecutive 9-min periods of watch. Two predictors of interest were cerebral blood flow velocity (CBFV), measured via transcranial Doppler ultrasonography (Warm & Parasuraman, 2007), and subjective state, as indexed by the Dundee Stress State Questionnaire (DSSQ; Matthews, et al; 2002). The results testify to the importance of assessing task-induced responses for predicting vigilance performance. They also indicate that forecasting vigilance performance is a complex endeavor requiring a set of multidimensional predictors. Specifically, multiple regression (R = .358) indicated that higher levels of CBFV in the left and right hemispheres and higher post-battery task engagement scores on the DSSQ during performance of the screening battery predicted perceptual sensitivity (A') during the final period of watch when performance deficiencies are most likely to occur. Predictions from a correlation of this magnitude, which accounts for 9.7 percent of the variance when adjusted for shrinkage, can lead to an increase in job success rate of 40 to 60 percent (Koelega, 1992; Rosenthal & Rubin, 1982). These findings were interpreted theoretically in light of a resource model of vigilance proposed by Davies & Parasuraman (1982).

Committee: Dr. Joel Warm (Advisor) Subjects:

MA, Kent State University, 2012, College of Arts and Sciences / Department of Psychological Sciences

Cognitive impairment is common among individuals with heart failure (HF). While the mechanisms linking cognitive dysfunction and heart failure are still being elucidated, structural brain changes and reduced cerebral perfusion have been implicated as important contributors. However, the limited research investigating these potential mechanisms has yielded mixed results. The current study examined the relationships among cardiac output, cerebral blood flow, and cognition, with a specific focus on cardiac output as a potential moderator of cognitive impairment. A total of 100 older adults with HF completed a comprehensive neuropsychological battery, a measurement of cardiac function (i.e., cardiac output), and transcranial Doppler ultrasonography to quantify cerebral blood flow indices (i.e., mean flow velocity and pulsatility index of the anterior, middle, and posterior cerebral arteries). Hierarchical multiple regression was used to determine whether cardiac output moderated the relationship between cerebral blood flow and cognitive performance in the domains of memory, executive function, attention/psychomotor speed, and language. A moderating effect of cardiac output was only observed for the relationship between mean flow velocity of the anterior cerebral artery for memory and executive performance. However, these results did not exhibit the expected pattern as higher levels of cardiac output with increasing mean flow velocity of the anterior cerebral artery was associated with decreased executive function and no change in memory performance. Moreover, cardiac output was not found to be a significant individual predictor of performance within these models, and blood flow velocity was only associated with memory performance. These findings suggest the associations among cardiac output, cerebral blood flow, and cognition in HF are more complex than originally suspected. It is possible these relationships were obscured by the relatively intact cognitive functi (open full item for complete abstract)

Committee: John Gunstad (Advisor); Mary Beth Spitznagel (Committee Member); Joel Hughes (Committee Member); John Updegraff (Committee Member) Subjects: Psychology

Doctor of Philosophy, Case Western Reserve University, 1993, Biomedical Engineering

A thermal perfusion system is developed to measure cerebral blood flow continuously and quantitatively, with thermistors placed on brain surface to minimize tissue damage. Heat transfer models for tissue and self-heated thermistor are used to compare sensitivity, resolution and dynamic response under different operating modes and boundary conditions. Simulation results indicate that large perfusion sensitivity requires large thermistor while fast dynamic response calls for small thermistor. Adiabatic condition at the tissue-environment interface can maximize perfusion sensitivity and minimize thermal interference. Theoretical framework for optimal probe and system design based on measurement requirements has been established through the steady-state relations between thermal output and perfusion. The system, with lock-in amplifiers and a thermistor for reference temperature, can detect temperature signal of 0.001°C caused by perfusion changes while accommodating baseline temperature variations on the order of 0.1°C. The perfusion sensitivity and dynamic response are tested in vitro and in vivo. Noise analysis indicates that thermal fluctuations in tissue and environment are much larger than electrical noise and are the major error source. Perfusion changes associated with arterial blood pressure changes caused by bolus norepinephrine injections are used to validate the system output during continuous heating. In vivo evaluation demonstrates that the dynamic response is adequate to follow transient perfusion changes before autoregulation and perfusion cycling around 0.1 Hz. A partial analytical solution of the heat transfer model is developed, resulting consistent relations between transient and continuous heating modes. Model parameters including perfusion are estimated by nonlinear least-squares fitting from the temperature response during transient heating. A calibration coefficient is obtained from the estimated parameters without varying perfusion at different l (open full item for complete abstract)

Committee: Gerald Saidel (Advisor) Subjects: Engineering, Biomedical