Arterial Spin-labelled MRI Analyses to Advance Adolescent Bipolar Disorder Research and Clinical Applications

Cerebral blood flow (CBF) is foundational to brain function in health and disease. Through three distinct analyses, the aim of this thesis is to extend current understanding of CBF in adolescent bipolar disorder and to enable future understanding of CBF in other brain diseases. CBF measurement can interrogate the putative vascular underpinnings of bipolar disorder, however, the extent of CBF changes in the early stages of the disease is unknown. ASL MRI allows non-invasive imaging of brain physiology, including CBF, and is especially valuable when invasive methods are inappropriate, such as in adolescent psychiatry. Yet, technical advancements have only recently supported wider availability of ASL and this thesis focuses on remaining opportunities to: 1) study the multivariate relationships of CBF between brain regions in health and disease and 2) continue technological advancement of ASL workflows for researchers and clinicians alike.In the first study of this thesis, I present an analysis of multivariate patterns of CBF, and their relationship to neuroanatomy, in a large group of adolescents with and without bipolar disorder. The results show differences between adolescents with and without bipolar disorder with respect to patterns of CBF and their correspondence to inter-regional relationships of brain anatomy. In the second study, I identified a multivariate CBF phenotype related to adolescent bipolar disorder. This analysis extends that of the first study by using patterns of CBF in a classification scheme based on participant diagnosis. In the third study, I develop a fast and automated CBF image synthesis algorithm to address a bottleneck in the workflow of advanced ASL MRI. I demonstrate a significant analysis speedup over a standard workflow, show capability of hemodynamic parameter uncertainty estimation, and present preliminary evidence of generalizability to specific acquisition parameters. This thesis employs three distinct ASL analyses to show multivariate phenotypes of CBF in adolescent bipolar disorder, and to support future study of CBF through image processing methods development. Together, these studies act toward understanding the physiological underpinnings of bipolar disorder, develop methods for CBF image analysis and synthesis, and support broad application of ASL in clinical neuroimaging research.

Department dc:contributor.department

Medical Biophysics

Year dc:date.issued

2022

Author dc:creator

• Luciw, Nicholas J

Advisor dc:contributor.advisor

• MacIntosh, Bradley J

• arterial spin labelling
• bipolar disorder
• cerebral blood flow
• deep learning
• magnetic resonance imaging

Statement dc:rights

• Attribution 4.0 International

Licence dc:rights.uri

• http://creativecommons.org/licenses/by/4.0/

Handle dc:identifier.uri

http://hdl.handle.net/1807/123344

OAI identifier oai:identifier

oai:utoronto.scholaris.ca:1807/123344