Methods of magnetization transfer MRI for assessing brain white matter damage

Activity: Examination and supervisionExternal Reviewer of PhD thesis/Opponent

Description

Magnetic-resonance-imaging (MRI) is one of the most important non-invasive techniques in Neuroimaging and is particularly appreciated for its high soft-tissue contrast. MRI assesses the magnetic property of protons as well as their chemical environment and acquires brain morphometry in high resolution of less than one millimeter. Moreover, MRI enables the assessment of functional activation, diusion, perfusion, metabolites and exchange-processes. In
diseases, such as multiple sclerosis (MS), MRI is used to detect in ammation and blood brain barrier disruptions, which might lead to neuronal loss and demyelination. In the early stage of the disease, such white matter (WM) changes cause an increased interstitial water content, which can be seen as hyperintense spots in fluid attenuated sequences. So-called white matter
hyperintensities (WMH) are a hallmark of MS and determine the clinical progression. However, histopathological studies revealed, that the WMH depict just the tip of the iceberg while the underlying pathology might be far more widespread. A higher sensitivity can be achieved using magnetization transfer (MT), a physical process based on the exchange of magnetization between water-protons and protons bound to macromolecules of lipids, such as myelin sheets. Remarkably, MT allows to assess microstructural changes also in the normal appearing white matter (NAWM) before WMH become visible.

This thesis studies changes in the NAWM using MT, by focusing on areas adjacent to cerebrospinal-fluid (CSF) and thus aiming at investigating the outside-in theory, which postulates that periventricular tissue damage in MS patients is caused by an invasion of toxic factors dissolved in the CSF. A gradual damage of NAWM was observed towards the ventricle in MS patients compared to healthy controls, by assessing the MT-ratio (MTR) in equidistant bands around the ventricle. Supporting the outside-in theory, this MTR-gradient was strongest in relapsing-remitting-MS (RRMS) patients, in whom it also correlated to cortical thickness. Remarkably, the MTR-gradient was also apparent in early MS patients. However, MTR is only a semiquantitative measure for MT in contrast to quantitative MT (qMT) approaches, that allow the estimation of specific parameters of the two-pool model. One such parameter is the relative amount of protons bound to macromolecules (bound pool fraction (BPF)), which has been identified as the strongest predictor for
myelin density. However, due to time constrictions, qMT sequences are not used in clinical
routine. An accelerated approach is based on the estimation of the biexponential decay of the longitudinal magnetization, which can be measured using a stimulated echo acquisition mode (STEAM) sequence. By considering inhomogeneities of the active transmit field and an additional quantitative T1 measurement, the biexponential decay can be reconstructed with one STEAM measurement using both spin and stimulated echoes. Illustrating how to
efficiently implement and holistically validate such an examination { making use of numerical simulations, phantom and in-vivo measurements { claims an important share in this thesis, targeting on making the assessment of the bound pool fraction feasible in the clinical routine.
Period2022 Jul 8
Examinee/Supervised personLukas Pirpamer
Examination/Supervision held at
  • Graz University of Technology
Degree of RecognitionInternational