Date of Award

December 2017

Degree Type


Degree Name

Master of Science



First Advisor

Mahsa Ranji

Committee Members

Yi Hu, Yougjin Sung, Thomas C. Chelimsky


Cytochrome C Oxidase, Heads-up Tilt Table Test, Hemoglobin, Muscle, Brain Tissue, Near-infrared Spectroscopy, Postural Orthostatic Tachycardia Syndrome (pots)





Parvathi Kadamati

The University of Wisconsin-Milwaukee, 2017

Under the Supervision of Professor Mahsa Ranji

Aims: Postural orthostatic tachycardia syndrome (POTS) is a type of chronic orthostatic intolerance, annually affecting around 500,000 young Americans. Symptoms of POTS include lightheadedness and persistent increase in heart rate with upright body posture [1-3]. It requires a medical diagnosis. Impaired cerebral oxygenation of patients with POTS has been reported [4]. The pathophysiology remains unclear, and research is needed to understand the underlying conditions that lead to POTS. The aim of this research is to design a medical device called Cytoximeter and apply it to conduct a study between POTS patients and healthy controls for objective monitoring and quantitative measurements.

Introduction: A custom build near-infrared spectroscopy (NIRS) device called Cytoximeter was constructed to monitor the blood oxygenation and the redox behavior of intact tissue’s Cytochrome C Oxidase (CCO), in clinical and research setting, noninvasively. The presence of hemoglobin absorption leads to complex algorithm implementation to separate the signals of the hemoglobin and CCO. Today we have different kinds of oximetry available, which provide information about the hemoglobin levels. However, the hemoglobin signals can only provide information regarding the changes of oxygen in the tissue. Monitoring CCO may give us information about the metabolic status of the tissue and intracellular levels of oxygen [5]. CCO is the final acceptor in the electron transport chain (ETC) and is an essential part of aerobic or anaerobic metabolism [3, 6]. CCO reduces by taking electrons in ETC cycle. This enzyme accepts electrons and changes to reduced state. The custom build optical device is designed to monitors the optical densities of the tissue by applying Beer-Lamberts law to monitor the change in concentration of these chemicals. This ability can give the NIRS many applications for research and clinical purposes. POTS is a clinical application for this device; a study was conducted to monitor the POTS patients and healthy control subjects to observe the difference in oxygenation levels between these two groups while undergoing the head up tilt table test.

Methods: I measured and compared the difference in the changes in oxyhemoglobin and deoxyhemoglobin by applying this Cytoximeter to POTS patients and healthy controls while undergoing the heads-up tilt. The device uses the optimal source to detector separations to acquire the CCO signal and change in oxygenation of hemoglobin signals, which uses the six wavelengths near-infrared spectroscopic design. Validation of the device includes conducting the phantom studies and employing new experimental protocols. In the clinical setting, the device was applied to the muscles and brain tissue of the patients with POTS and Epilepsy under the standard care of neurological examiners.

Results: The results showed significant differences in deoxyhemoglobin, oxygenation change and blood volume between the control subjects and POTS patients. We found that the arterial system is less compliant with the inability to receive additional blood volume in POTS patients. Results of the phantom studies that I conducted showed that the device was able to monitor the real-time changes in oxygenation of blood and the redox state of CCO.

Conclusion: The custom build Cytoximeter successfully monitored the hemoglobin signal along with the CCO signal. The device provided an objective means of measuring and physiological findings in understanding the underlying reasons of POTS. Further work is required to determine whether the calf muscle activation of POTS patients is comparable to the healthy controls.

Available for download on Wednesday, January 09, 2019