Bijaya Thapa Thesis Defense 08/28/2017

Thesis Defense

Bijaya Thapa

Monday, August 28th
3:00PM (219 JFB)

Title: Advancement in Biomedical Magnetic Resonance Imaging & Spectroscopy

This dissertation comprises two separate studies: 1) efficacy of an anabolic steroid, oxandrolone, on the energy utilization of the heart of a lamb born with single ventricle (SV) physiology using ^31 P MR spectroscopy (MRS) and 2) signal behavior of ultra-high-b radial diffusion weighted imaging (UHb-rDWI) in healthy subjects and multiple sclerosis (MS) patients.

SV infants have the highest mortality of all other infants that have congenital heart defects. Their inability to gain weight appropriately may be due to high cardiac energy requirements from their shunt dependent physiology. We hypothesize that, oxandrolone which is already known to markedly improve the nutritional state of burn patients, will improve the energy utilization in the heart. We tested our hypothesis on SV modelled lambs using ^31 P MRS, home built ^1 H/^31 P double tuned radio frequency (RF) coil, and ^1 H and ^31 P T/R switches. We monitored cardiac energy in the lamb by quantitatively evaluating the first order forward reaction rate (kf) of the creatine-kinase (CK) reaction in the heart. We also performed cine magnetic resonance imaging (MRI) to study the dynamic function and loading of the left ventricle by evaluating* *ejection fraction (EF). Our study shows some improvement in both kf and EF.

Spinal cord injury due to pathologies, such as MS, may include demyelination and/or axonal damage and lead to varying degrees of neurologic deficit, which can cause a devastating impact on physical and mental health. Non-invasive imaging biomarkers for earlier disease detection and monitoring in the follow-up and treatment stages would be a significant advancement in patient care. MRI enables superb contrast and spatial resolution of the spinal cord; however, conventional MRI sequences (T1- and T2-weighted) are unable to characterize the elements of early/active lesion formation, or the evolution of these lesions. Moreover, imaging of the cervical spinal cord (CSC) is technically challenging because of the low signal to noise ratio from the small cross section of the cord, susceptibility artifact due to tissue-bone interface, and motion induced artifact from breathing and swallowing. To resolve these challenges, we used the UHb-rDWI technique that greatly reduces the geometric distortion by implementing reduced field of view in the phase encoding direction and the motion induced artifact using single shot acquisition and a CSC dedicated phased array RF coil. We studied the behavior of UHb-rDWI signal over the range of b-values from 0 s/mm2 to 7348 s/mm2 in the CSC of healthy and MS subjects over multiple time points. In the normal CSC, the signal decays fast at low b and slow with high decay-constant (DH) at UHb (b>4000 s/mm2). Our results also show that UHb-rDWI is consistent over time for imaging of major white matter tracts in the normal CSC. In MS patients, the region affected by active lesions revealed a marked decrease in signal intensities and increase in DH in UHb region, which approach towards normal values in later time points consistent with the clinical measurement of recovery. UHb-rDWI could, therefore, be used for establishing an imaging biomarker to distinguish inflammation, demyelination, and axonal loss in the CSC. In addition, UHb-rDWI has the potential to monitor the disease course therapeutic outcomes.

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