Loreen Ruhm1, Johanna Dorst1, Nikolai Avdievich1, and Anke Henning1,2
1Max Planck Institute for Biological Cybernetics, Tübingen, Germany, 2UT Southwestern Medical Center, Dallas, TX, United States
Synopsis
31P Magnetic Resonance Spectroscopic
Imaging (MRSI) is a non-invasive method that can reveal information about the
energy and phospholipid metabolism. In this work, we investigate the
differences in signal amplitudes of different 31P metabolites
between grey and white matter tissue in the human brain. We acquired highly resolved
31P MRSI data at an ultrahigh field strength B0 of 9.4 T
from the brain of six healthy volunteers. For the quantification of the 31P
MRSI data, different correction were applied to the signal amplitudes.
Purpose
To
present 31P metabolic maps acquired at 9.4 T from the human brain of
healthy volunteers and investigate differences between grey and white matter
tissue.Introduction
Phosphorus
magnetic resonance imaging (MRSI) can reveal important information about the
energy and phospholipid metabolism as well as intracellular pH without an
invasive intervention1. However, 31P MRSI has a
relatively low signal sensitivity compared to 1H MRI/MRSI and a corresponding
low spatial resolution. A way to address this problem is to go to a very high
magnetic field B0. In this work, we present phosphorus metabolic
maps acquired from the brain of healthy human volunteers at an ultrahigh field
strength of 9.4 T with a nominal resolution of 0.59 ml which was not yet
reported for 31P MRSI. Different signal corrections have been
applied to be able to investigate differences in 31P signal
amplitudes between grey and white tissue of the healthy human brain. Method
The
data was acquired from a 9.4 T whole body MRT (Siemens Healthineers, Erlangen,
Germany) using an in-house built double tuned 31P/1H
array coil (8TxRx/2Rx for 31P, 10TxRx for 1H)2.
Informed consent was obtained for all volunteer measurements. The data was
acquired from six healthy volunteers.
Prior to each in vivo measurement, a B1+
calibration was performed with a Bloch-Siegert shift based single voxel spectroscopy
sequence (TAcq = 160 sec). For
31P MRSI, a 3D chemical shift imaging (CSI) sequence3
with a total measurement time of 74 min and the following parameters was used:
FoV (180x200x180) mm3, grid size (28x30x13x512), TR = 250 ms, α = 25 deg, 16 averages, broadband sinc pulse
excitation, Hamming weighted acquisition, acquisition bandwidth = 5 kHz and
nuclear Overhauser enhancement (nOe) with rectangular saturation pulses4.
The effective voxel size is approximately 3.7 ml. The sinc pulse was optimized
in a separated phantom measurement. Different time bandwidth products (TBP)
and pulse durations (Tp) were tested for the sinc shaped excitation
pulse to find the optimal pulse.
The analysis of the data was performed in
Matlab using a self-implemented fitting routine based on the AMARES algorithm5
that considers Voigt line shapes. A Tucker tensor decomposition of the
spectrospatial data was used for noise reduction6,7. Prior to denoising, corrections for B0 and phase shifts were performed based
on a fit of the PCr (phosphocreatine) resonance.
Quantification results were corrected for T1
relaxation and nOe enhancement factors based on values taken from earlier
publications4,8. To correct for the sensitivity profile of the coil,
the measured signal amplitudes are ratios to the summed signal over all resonance.
The corresponding summed signal reference map was smoothed applying a Low Rank
approximation9.Results and Discussion
Fig. 1 shows the measured excitation
profiles of the tested sinc shaped pulses measured in a phantom measurement.
Among the detectable resonances, α-adenosine triphosphate (α-ATP) has the largest chemical shift with -7.52 ppm1.
To achieve a homogeneous excitation profile over a bandwidth of ± 7.52 ppm, a sinc shaped pulse with Tp = 2
ms and TBP = 8 was used in our 3D 31P MRSI implementation.
Fig. 2 shows the sum over all
detected metabolites and the corresponding low rank smoothed image of volunteer
#1. The later was used for normalization of the spectra and resonance
amplitudes to correct for the sensitivity profile of the coil. The underlying
assumption is that the total phosphate pool is constant1.
Fig. 3 shows the acquired images of
phosphocreatine (PCr), α/γ-adenosine triphosphate (α/γ-ATP), glyceryl-3-phosphorylcholine (GPC) and phosphorylethanolamine (PE) for all six volunteers as ratios to the summed
signal.
Fig. 4 shows the final result of the
analysis. Shown is the spectrum summed over a region with high grey matter content
as well as a region with high white matter content for volunteer #1 as well as
the comparison of grey and white matter dominated areas for all six volunteers.
The summed spectra were normalized to the number of voxels included in the area
as well as the summed phosphate signal as shown in Fig. 2. The final amplitudes
of the phosphate metabolites shown in Fig. 4 were estimated from the summed
spectra and corrected for nOe enhancement and T1 saturation.
As only six volunteers could be
evaluated so far, a profound statistical analysis is not yet possible. However,
findings from former publications10,11 indicated a lower signal of
PME (phosphomonoester, e.g. PE) and PCr in white matter whereas ATP and PDE
(phosphodiester, e.g. GPC) showed a higher signal in white matter. This
findings are very consistent with the presented results.
In the future, a further analysis of
these differences is planned with a higher number of volunteers. The aim is to
probe the stability of 31P MRSI in detecting signal differences
between different tissue types to move towards clinical application.Conclusion
We
successfully acquired 31P metabolic maps with a high nominal spatial
resolution of 0.59 ml which
has not been achieved before. Further, differences between grey
and white matter signal amplitudes could be presented for different 31P
metabolites after correcting for coil sensitivity, nOe enhancement and T1
saturation. It could be shown that the results are consistent with earlier
publications.Acknowledgements
Funding
by the European Union (ERC Starting Grant, SYNAPLAST MR, Grant Number: 679927) and
by the Cancer Prevention and Research Institute of Texas (CPRIT) (Grant Number:
RR180056) is gratefully acknowledged.References
[1] de Graaf RA. In Vivo
NMR Spectroscopy – 2nd Edition: Principles and Techniques. WILEY
2007. ISBN: 978-0-470-02670-0
[2] Avdievich N, Ruhm L,
Dorst J, Henning A. Double-Tuned 31P/1H Human Head Array with High Performance
at Both Frequencies for Chemical Shift Spectroscopic Imaging (CSI) at 9.4 T.
In: Proceed. Of the ISMRM (Montreal) 2019. Abstract nr. 0433.
[3] 31P CSI of
the human brain in healthy subjects and tumor patients at 9.4 T with a
three-layered multi-nuclear coil: initial results. Magn Reson Mater Phys 2016;
29: 579 – 589
[4] Ruhm L, Dorst J, Avdievich N, Henning A. High-Resolved
nOe-Enhanced 31P MRSI of the Human Brain at 9.4T. In: ISMRM Workshop on
Ultrahigh Field Magnetic Resonance: Technological Advances, Translational
Research Promises & Clinical Applications (2019). Dubrovnik, Croatia.
[5] Vanhamme L, van den
Boogaart A, Van Huffel S. Improved method for accurate and efficient
quantification of MRS data with use of prior knowledge. J Magn Reson 1997;
129(1): 35 – 43
[6] Brender JR, Kishimoto
S, Merkle H, Reed G, Hurd RE, Chen AP, Ardenkjaer-Larsen JH, Munasinghe J,
Saito K, Seki T, Oshima N, Yamamoto K, Choyke PL, Mitchell J, Krishna MC.
Dynamic Imaging of Glucose and Lactate
Metabolism by 13C-MRS without Hyperpolarization. Scientific Reports 2019;
9:3410
[7] Tensor Toolbox version
3.1 by Bader BW, Kolda TG, Acar E, Dunlavy DM et al. Copyright 2019, Sandia
National Laboratories
[8] Raju S, Scheffler K,
Pohmann R. T1 values of phosphorus metabolites in the human visual cortex at
9.4 T. Magnetic Resonance Material in Physics, Biology and Medicine, 30
(Supplement 1). S243 – S244. 34th Annual Scientific Meeting of the
European Society for Magnetic Resonance in Medicine and Biology (ESMRM 2017),
Barcelona, Spain.
[9] Nguyen HM, Peng X, Do MN, Liang ZP.
Denoising MR Spectroscopic Imaging Data With Low –Rank Approximations. IEEE
Trans Biomed Eng 2013; 60(1): 78 – 89
[10] Dudley J, Chu W, Fugate
E, and Lee J. Tissue dependent metabolism in the human brain suggested by
quantitative phosphorus-31 MRSI. Journal of Spectroscopy and Dynamics 2014;
4(19)
[11] Hetherington H, Spencer JVDD, and Pan J.
Quantitative 31P Spectroscopic Imaging of the Human Brain at 4
Tesla: Assessment of Gray and White Matter Differences of Phosphorcreatine and
ATP. Magentic Resonancein Medicine 2001; 45:46–52