Date of Award
2007
Degree Type
Thesis
Degree Name
Doctor of Philosophy
Program
Medical Biophysics
Supervisor
Dr. Neil Gelman
Abstract
Neonatal hypoxic-ischemic brain injury often leads to severe neurodevelopmental impairment. Early detection of injury is important for the clinical management of neonates as well as monitoring of neuroprotective therapies, which are currently being investigated. ■
Diffusion-weighted imaging (DWI) plays an important role in the assessment of neonatal patients with clinical indications of hypoxic-ischemic encephalopathy (HIE). With the goal of improving efficacy of DWI in neonatal HIE, the first two parts of this thesis are (i) the characterization of the evolution of the apparent diffusion coefficient (ADC) in neonates with HIE and poor outcome (particularly the postnatal age when ADC values within brain regions of the injured neonates cannot be distinguished from healthy neonates (pseudo-normalization time), and (ii) the development of a post-processing motion correction technique in diffusion-weighted and diffusion tensor images. The third part of the thesis uses an animal model to characterize the cerebral metabolic response to HI by combining near-infrared spectroscopy (NIRS) measurements of cerebral metabolic rate of oxygen (CMRO2) with 31P magnetic resonance spectroscopy (MRS) measurements of high- energy metabolites.
i) The relationship between the ADC and postnatal age was estimated for neonates with HIE and poor outcome (death or severe disability) for several brain regions using a linear regression analysis. Pseudo-normalization times were determined (a) from the intersection of the regression lines for the HIE and control groups, as well as (b) from a small subgroup (N = 4) of neonates scanned at two or more time points by measuring the intra-subject ADC changes between the two scans. Pseudo-normalization times from the regression analysis ranged from 8.3±1.9 days to 10.1±2.1 days, with slightly (approximately one day) longer values obtained from the intra-subject analysis. We conclude that although abnormally decreased ADC values may be evident from approximately two days to almost one-week postnatal age, abnormally elevated values may not be apparent until late in the second week of life.
III
ii) Despite the increased susceptibility to motion artifacts over traditional single shot echo planar imaging (EPI) we chose segmented EPI due to its advantages for imaging at higher field strengths (3.0 T). These advantages include reduced blurring and distortion, as well as lower acoustic noise levels (especially important for safety of neonates). In this thesis I developed and quantitatively assessed the efficacy of a post-processing technique for motion artifact reduction of eight-segment EPI involving phase correction by nonlinear optimization, alone and in combination with a novel method of utilizing a second data set (referred to as segment data swapping). These methods were applied to three-directional DW segmented EPI data obtained from 13 sedated neonates and nine-directional DTI data from three unsedated neonates. Median, artifact to signal ratio values obtained from neonatal three-directional DWI, using nonlinear optimization alone and in combination with segment data swapping were 2.8 % and 1.9 %, respectively. Similar results were obtained for DTI. Thus, this technique provides effective motion correction for neonatal DWI at 3.0 T, especially when used in conjunction with segment data swapping.
iii) Recent developments in neuroprotective therapies indicate a need for early detection of hypoxic-ischemic brain injury, within the first hours following birth. Previously, using NIRS, a persistent reduction in CMRO2 was measured within the first six hours following hypoxia-ischemia (HI) in newborn piglets. In our study, following HI, CMRO2 reduced significantly and persistently by 24 ± 2 % compared to controls. In contrast, we observed a general recovery of high-energy phosphate levels by 3.5 h after HL Depressed CMRO2 despite recovery of high-energy metabolites indicates the presence of injured tissue with reduced energy demand during the first hours following HL
Recommended Citation
Winter, Jeff D., "Development AND CHARACTERIZATION OF NON- INVASIVE Measures OF NEONATAL HYPOXIC- ISCHEMIC Brain INJURY" (2007). Digitized Theses. 4987.
https://ir.lib.uwo.ca/digitizedtheses/4987