IMAGING T1, T2 AND MYELIN WATER FRACTION IN THE POST-MORTEM MULTIPLE SCLEROSIS CENTRAL NERVOUS SYSTEM
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The subject of this thesis is the use of Magnetic Resonance (MR) Imaging to
quantify biometric MR indices in the Multiple Sclerosis (MS) fixed post-mortem
central nervous system (CNS) tissue. Evaluating these indices in fixed tissue
allows for the use of histology to verify the findings of MRI. However, it must first
be discovered if the indices can be evaluated in fixed post-mortem spinal cord
tissue. There is very little literature in this specific area, though some in the fixed
brain, the results of which have been assumed to be equivalent in the spinal
cord without proof. Therefore, the methodology must first be verified before the
consideration of any index as useful and translatable to in-vivo spinal cord.
This thesis concentrates on the evaluation of MR relaxometry methods using the
indices T1 and T2 by themselves and to evaluate the myelin content of fixed
post-mortem CNS tissue. The Carr-Purcell-Meiboom-Gill (CPMG) and Multicomponent
Driven Equilibrium Single Pulse Observation of T1 & T2 (mcDESPOT)
sequences are used to calculate T1, T2 and the Myelin Water Fraction (MWF)
which is believed to be proportional to myelin content in the CNS. This is
performed at 3T in a clinical scanner and at 7T in a small animal and wholebody
scanner. The methods are first evaluated for use in fixed post-mortem CNS
tissue. The two myelin measurement methods are then compared to
histological staining if appropriate and where available to verify that the results
obtained are proportional to myelin content.
The T1 and T2 values in fixed tissue were found to be shortened in fixed tissue, T2
values were so short as to be at the limits of measurement by a clinical scanner,
and values converged in white and grey matter, and therefore contrast was
found to be limited between these tissues. Proton density images provided the
most contrast between tissues. However, even with shortened T2 values, the
CPMG sequence was able to identify the myelin water component in fixed
tissue. The mcDESPOT algorithm struggled to separate the myelin water
component due to clinical scanner limitations and the shortened, converging
T1 and T2 values. However, the mcDESPOT algorithm was successful in discerning
the myelin water component in the high signal situation of a small bore 7T peclinical
scanner.
An evaluation was then made of the usefulness of these indices for translation
into clinical imaging. The CPMG sequence was found to be proportional to
myelin content under all conditions, and therefore useful for disease monitoring
in demyelinating diseases. The mcDESPOT sequence, was found to be
proportional to myelin in some conditions, and is likely to be useful for
monitoring myelination, though the sequence could not be fully validated in
this thesis.
Authors
McDowell, Amy RebeccaCollections
- Theses [4235]