Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Medical Biophysics

Supervisor(s)

Dr. Jean Théberge

Abstract

Proton magnetic resonance spectroscopy (MRS) non-invasively measures regional human brain chemistry in vivo, providing concentration estimates for several metabolites in a pre-selected region of interest. MRS has been applied to investigations of disease-related metabolic and neurochemical alterations in schizophrenia since the early 90’s.

The objective of this research is to implement a metabolite-selective MRS method to quantify endogenous concentrations of human brain serine. Serine is a naturally-occurring amino acid and an important co-modulator of the N-Methyl D-aspartic Acid (NMDA) glutamate receptor. Glutamate abnormalities have been implicated in the pathophysiology of schizophrenia, especially its so-called negative and cognitive symptoms, which can be relieved by D-serine supplements.

Measurements of serine have been impossible using standard MRS due to its low concentration and strongly coupled spins. In this thesis, we implement and test an advanced MRS pulse sequence, called DANTE-PRESS, using a narrow band radiofrequency (RF) pulse to isolate the serine signals from the human brain spectra for the first time on a 3.0 Tesla clinical scanner.

Test-retest reliability of in vitro serine measurements in brain-mimicking samples was verified using ten repeated acquisitions from two serine samples with concentrations of 0.732 mM (similar to “in vivo”) and 1.464 mM (“double in vivo”) at baseline and one week later. Within- and between-session reproducibility was measured with the coefficient of variation (CV) and one-way ANOVA, respectively. Average serine “in vivo” concentration at baseline, one week later, “double in vivo” at baseline, and one week later were 1.13 ± 0.09 (CV = 8.3%), 1.06 ± 0.10 (CV = 9.9%), 2.18 ± 0.13 (CV = 5.7%) and 2.23 ± 0.14 (CV = 6.5%), respectively.

The thesis also presents a 3.0 Tesla application of DANTE-PRESS in a human brain region relevant to schizophrenia as proof-of-concept. Future studies can extend the work to implementation of DANTE-PRESS at 7.0 Tesla and in vivo test-retest.

Available for download on Monday, July 31, 2017


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