Document Type


Date of Degree

Fall 2018

Access Restrictions

Access restricted until 01/31/2021

Degree Name

PhD (Doctor of Philosophy)

Degree In

Biomedical Engineering

First Advisor

Kaczka, David W

First Committee Member

Tawhai, Merryn H

Second Committee Member

Hoffman, Eric A

Third Committee Member

Christensen, Gary E

Fourth Committee Member

Reinhardt, Joseph M


The goal of lung-protective mechanical ventilation is to provide life-sustaining support of gas exchange while minimizing the risk of ventilator-induced lung injury. Multi-frequency oscillatory ventilation (MFOV) was proposed as an alternative lung-protective modality, in which multiple frequencies of pressure and flow oscillations are delivered simultaneously at the airway opening and allowed to distribute throughout the lung in accordance with regional mechanical properties. The distribution of oscillatory flow is frequency-dependent, such that regions overventilated at one frequency may be underventilated at another. Thus the central thesis of this work was that ventilation heterogeneity is frequency-dependent, and therefore ventilation with multiple simultaneous frequencies can be optimized to reduce the risk of ventilator-induced lung injury. Simulations in computational models of distributed oscillatory flow and gas transport demonstrated the sensitivity of regional ventilation heterogeneity to subject size, ventilation frequency, and injury severity. Although the risk of injury in the model associated with strain or strain rate individually was minimized by single-frequency ventilation, the risk of injury associated with mechanical power in lung parenchymal tissue was minimized by MFOV. In an experimental model of acute lung injury, MFOV was associated with reductions in the magnitude and spatial gradient of regional lung strain estimated by four-dimensional CT image registration, as well as increased rates of regional gas transport estimated by wash-in of xenon tracer gas. In conclusion, computational models demonstrated the potential for optimization of MFOV waveforms, and experimental trials demonstrated evidence of improved regional ventilation during MFOV.


Acute lung injury, Computational modeling, Mechanical ventilation, Medical imaging, Respiratory mechanics


xiii, 184 pages


Includes bibliographical references (pages 162-184).


Copyright © 2018 Jacob Herrmann