Myelin is a multi-lamellar membrane that surrounds the axon of most nerve cells, forming an electrically insulating layer, which increases the speed of action potential transmission by a factor of 10 to 100. Thus, myelin is of utmost importance for complex neuronal functions. In demyelinating diseases such as multiple sclerosis, the myelin sheath of the neurons is damaged. For the evaluation of disease progression and for therapy monitoring (e.g. remyelination), non-invasive mapping of the myelin content is desirable.
In magnetic resonance imaging (MRI), myelin has very short transverse relaxation times (50 µs < T2* < 1 ms). In clinical MRI, the signal is acquired after a few milliseconds so that myelin is not directly detectible. Only indirect, mostly non-quantitative estimates of the myelin content are currently available.
An approach to directly detect myelin is based on ultrashort echo time (UTE) pulse sequences . These pulse sequences enable the detection of fast decaying MRI signals that originate from non-water protons in the myelin sheaths. A two-dimensional inversion recovery (IR) UTE MRI pulse sequence for imaging of myelin in human brain has recently been proposed for a 3 Tesla MRI system . A study with multiple sclerosis patients indicated that the IR-UTE sequence is able to identify the presence of demyelination .
UTE imaging techniques are currently not standard on clinical MR systems. In addition, they are very susceptible to inaccuracies in the spatial encoding process. The inaccuracies can be caused by imperfections of the MRI system and by eddy currents due to the required fast switching of the magnetic field gradients and high gradient amplitudes. This often results in image artifacts such as blurring. For clinical research, a fast 3D UTE technique that enables imaging of the whole brain with an isotropic spatial resolution – similar to a 3D MP-RAGE pulse sequence – would be highly valuable.
This project is focused on implementing such a sequence and on evaluating its potential for clinical and preclinical research at 7 Tesla. It shall enable non-invasive mapping of the myelin content (Fig. 1). Different methods to suppress signal from long T2* components will be evaluated. Techniques to map inaccuracies of the spatial encoding process will be applied. The inaccuracies will be accounted for in the image reconstruction to achieve high image quality (Fig. 2).
Figure 1. Simulated MRI signal response of different tissue types in the brain at the steady-state of an IR-UTE sequence.
By subtraction of both readouts, the suppression of the remaining white matter (WM) and gray matter (GM) signals shall be achieved, while isolating the fast relaxing myelin (ML) signal from the first readout.
Figure 2. Images of a resolution phantom acquired with an UTE technique.
a) Image reconstruction was performed using the expected k-space trajectories. b) Image reconstruction was performed using the measured k-space trajectories. The use of measured k-space data points for the image reconstruction leads to markedly improved image quality.
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Magnetic resonance imaging of myelin using ultrashort Echo time (UTE) pulse sequences: Phantom, specimen, volunteer and multiple sclerosis patient studies.