Date of Award
5-2-2022
Degree Name
Doctor of Philosophy (PhD)
Degree Type
Dissertation
Abstract
Due to advances in clinical medicine, more children currently diagnosed with a brain tumor become long-term survivors after treatment than in previous decades. As the number of long-term survivors of pediatric brain tumors increases, clinicians and caretakers focus more attention on improving the quality of life of these patients. Unfortunately, a significant proportion of long-term survivors of pediatric brain tumors have cognitive deficits, which reduce their quality of life. Cognitive tests prior to therapy are critical for accurately assessing a patient’s risk of cognitive decline because they provide a pre-treatment baseline for assessing how host, tumor, and treatment factor interact to produce deficits. However, comprehensive assessments of cognitive function are infrequently performed prior to treatment because of the difficulty of incorporating cognitive tests into the clinical work flow. Functional connectivity (FC) measurements have been shown to correlate with neurologic function (e.g. cognitive and motor deficit) in many diseases and can easily be obtained prior to brain tumor treatment. Before the assessment of cognitive function with FC measurements can be included in the standard of care for brain tumor patients, additional studies are needed to understand how host, tumor, and treatment-related factors interact to modulate the association between FC measurements and neurologic performance. However, human studies are unlikely to have the statistical power to determine the relationships between clinical factors, FC measurements, and neurologic function due to the difficulty of enrolling a large number of human subjects while controlling for heterogeneities in tumor type, tumor location, treatment strategies, and environmental factors. Fortunately, mouse studies can control for these variables in a large number of genetically identical specimens. Furthermore, FC measurements with high signal-to-noise ratios can be obtained more cost-effectively with optical-based neuroimaging techniques than with magnetic resonance imaging. Thus, this dissertation explores interactions between tumor-related factors, FC measurements, and neurologic function in a mouse brain tumor model using optical-based neuroimaging techniques. This study demonstrates the following: 1) Altered hemodynamics contribute to FC change in local but not remote functional networks as brain tumors grow; 2) tumor-related factors differentially modulate mechanisms that alter FC measurements; and 3) tumor-related factors alter the strength and timing of the relationship between FC measurements and behavior in a network-specific manner. This work lays the foundation for future studies that investigate how host-, tumor-, and treatment-related factors interact to regulate the relationship between FC measurements and neurologic function. The knowledge obtained from this dissertation could help personalize interventions and improve outcomes in long-term survivors of pediatric brain tumors.
Language
English (en)
Chair
Joseph Culver
Committee Members
Joshua Rubin