Luke A. Reynolds1, Alex L. MacKay1,2,3, and Carl A. Michal1
1Physics & Astronomy, University of British Columbia, Vancouver, BC, Canada, 2Radiology, University of British Columbia, Vancouver, BC, Canada, 3MRI Research Centre, University of British Columbia, Vancouver, BC, Canada
Synopsis
Adiabatic pulses are
commonly used in clinical MRI due to their insensitivity to B1 inhomogeneity
and uniform flip angle over a selected bandwidth. When applied to white matter,
they are generally assumed to saturate the magnetization of the non-aqueous
protons in myelin. We performed
adiabatic inversion recovery experiments on bovine brain in vitro using a solid state NMR spectrometer to directly observe
the effects of adiabatic inversions on the non-aqueous signal. Substantial non-aqueous
magnetization remains after typical adiabatic pulses. The state of the
non-aqueous magnetization seriously impacts measurement of T1,
yielding values dependent on the form of inversion pulse used.
Introduction
Soft pulses are ubiquitous
in clinical MRI because of their low energy deposition and selective excitation
bandwidth. Adiabatic pulses are modulated in amplitude and frequency such that
all spins within a selected bandwidth are flipped uniformly. It is often
assumed that adiabatic pulses saturate, or suppress, the non-aqueous proton
magnetization in white matter tissue1,2. The state of this
magnetization plays an important role in relaxation dynamics. While a consensus
has emerged that T2 relaxation measurements in white matter in vivo
can be understood in terms of a two-pool model3,4, conflicting
reports of the number of components required to meaningfully describe T1
endure5-9.
The goal of this study was to test the assumption that typical adiabatic
pulses saturate non-aqueous magnetization in white matter by directly measuring
the non-aqueous proton signal after adiabatic inversion and monitoring the
effects of the non-aqueous magnetization’s initial state on determinations of T1. Methods
Samples: We obtained an unfrozen bovine brain (Innovative Research – Novi,
MI, USA) approximately 30 hours after harvest. Tissue samples were immediately
extracted and sealed in 5mm NMR tubes with proton-free o-ring and caps . Two
samples were collected from the splenium of the corpus callosum weighing 53.6mg
(WM1) and 45.9mg (WM2) and one from frontal white matter weighing 67.7mg (WM3).
All experiments were performed within 36 hours of receiving the brain.
Experiments: Experiments were performed in a 360MHz (8.4T) NMR magnet using a
home-built spectrometer. Sequences used were (Fig. 1): inversion recovery with
FID (IR-FID) or CPMG acquisition (IR-CPMG). 30 inversion times, TI= 10µs - 10s,
and a 10s recycle time were used. Echo spacing (TE) was 2ms with 256 echoes obtained.
Three types of inversion
pulse were used. A ‘hard’ ~8µs rectangular pulse inverted all proton
populations. A 3ms three-lobe sinc pulse yielded a 1.1kHz excitation bandwidth, inverting only
the aqueous protons. Finally, an adiabatic hyperbolic secant (AHS) pulse was matched
to clinically relevant parameters1 – 10ms length, 750Hz maximum
amplitude, β 730s-1 10, and
4kHz bandwidth frequency modulation.
Analysis: IR-FID: The inversion recovery data were fitted to single
or double exponential decays using a non-linear least squares (NNLS) algorithm
(‘lsqnonlin’, MATLAB) to extract T1 values.
IR-CPMG:
CPMG echo amplitudes were fitted to a superposition of exponentials, $$$\sum_{i}f_{i} * exp(-TE/T_{2,i})$$$, using a regularized
NNLS algorithm (‘lsqnonneg’, MATLAB) to extract T2 values. Myelin
water fraction (MWF) was computed as the proportion of coefficients for $$$\frac{T_{2} < 40ms}{\sum T_{2}}$$$11.Results
Inversion Efficiency: IR-FID spectra from short TI (Fig. 2) show that
the hard pulse effectively inverted both aqueous and non-aqueous magnetization,
but it is clear that the adiabatic inversion left much of the dipolar broadened
non-aqueous magnetization along B0. When normalized to fully
equilibrated spectra, 48% of the non-aqueous signal (interpreted as -20kHz <
S < -1.8kHz & 0.8kHz < S < 20kHz) remained.
T1 Relaxation: IR-FID recoveries for the hard pulse inversion
were much more nearly single exponential (RMS misfit 0.6% maximum amplitude)
than for either adiabatic or sinc inversions (RMS misfits 3% and 5%
respectively), (Fig 3). More importantly, the best fit T1 of aqueous
amplitudes: 1.66 ± 0.02s, 1.38 ± 0.08s, and 1.25 ± 0.11s for the hard,
adiabatic, and sinc inversions respectively, were significantly different.
Applying two-component fits to the adiabatic and sinc cases provided better
fits by introducing a short time component and shifting the long component closer
to the single-component case (T1 = 1.59 ± 0.01s & 64 ± 4ms and 1.58
± 0.02s & 65 ± 4ms respectively).
T2 Relaxation: NNLS fitting generated similar T2
distributions (Fig. 4) for each inversion case. The three peaks are interpreted
to originate in the intra/extracellular water pool (T2 = 64ms) and
the myelin water pool (T2 = 26ms & 9.6ms). The MWF, 11.6%, was
found to be comparable to previous studies9,12.Discussion
These results demonstrate
that adiabatic inversion pulses do not saturate the non-aqueous proton magnetization.
The state of the non-aqueous magnetization has clear effects on determinations of T1. Single
exponential fits fail to consider effects of magnetization exchange between the
different aqueous and non-aqueous proton pools. When the populations are
prepared in different non-equilibrium states with soft pulses, magnetization
exchange rapidly equalizes the spin polarization in different pools giving the
appearance of a T1 that is faster than would be measured with
uniform inversion. With two-component fits, this manifests as the appearance of
a short T1 component13,14, which in this case was
measured to be approximately 65ms.
B1
inhomogeneity and incomplete spoiling have previously been attributed to
discrepancies in T1 mappings15. Neither factor is
significant here – B1 inhomogeneity in our system was approximately
1 part in 120 (Fig. 5), yet we still measured discrepancies in T1.
While B1 homogeneity and incomplete spoiling play significant roles
in MRI settings, it is evident that more fundamental dynamics need also be
considered to accurately reflect the system. Alternate treatments such as the
four-pool model have shown to be an effective step in the right direction8,9,12,16.Conclusion
We have shown that the
non-aqueous proton population in white matter is not completely saturated by
adiabatic inversion pulses, contrary to common assumption. This effect introduces
complex magnetization dynamics that are often overlooked in T1
relaxation measurements. Acknowledgements
No acknowledgement found.References
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