3876

Multi-pulse Sodium Magnetic Resonance Imaging for Multi-compartment Quantification in Brain at 7T
Martin Gajdošík1, Alina Gilles1,2, Ivan Kirov1, and Guillaume Madelin1

1Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York City, NY, United States, 2Institute of Radiology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany

Synopsis

We propose a new approach to investigate intra- and extracellular sodium in vivo. In this preliminary study we could differentiate brain compartments and provide an estimate of intracellular and extracellular sodium concentrations as well as intracellular, extracellular and cerebrospinal fluid volume fractions.

Introduction

The sodium cations (23Na+) play a major role in many fundamental physiological functions in human tissues1. The level of intra- and extracellular sodium concentrations (IC≈10-20 mM and EC≈140 mM, respectively)1,2 is tightly regulated in healthy mammalian tissue. Alterations in the distribution of sodium across the cell membrane may therefore be indicative of pathological conditions, either due to disease or during cell damage induced by therapy.

Sodium MRI is challenging, as the resulting images generally suffer from low signal-to-noise ratio. The signal is approximately 20000 times lower than the 1H signal in vivo, which makes ultra-high magnetic fields and lower resolutions necessary to increase SNR. Most of sodium MRI studies investigate the total sodium signal which therefore lack specificity about the origin of sodium signal variations and their link to valuable metabolic information3.

The compartments in the brain differ in their relaxation times and are assumed to correspond to the IC, EC, and the cerebrospinal fluid (CSF) compartments (compartments #: 1, 2 and 3). Inspired by MR fingerprinting4, with a multi-pulse sequence acquisition (e.g. 15 pulses), and a quantification method based on sodium spin 3/2 dynamics simulation, we could theoretically separate the sodium signal from these different compartments in human brain tissue in vivo. The separation with correction on water fraction maps5 could allow a quantitative estimation of IC sodium concentration (C1) as well as the volume fractions α1, α2 and α3 of the brain compartments.

In this pilot study, we present a proof-of-concept of the multi-pulse quantification method on a three-compartment phantom with known sodium concentration and volume fractions and its application to brain in vivo using a four-compartment brain tissue model at ultra-high field of 7T.

Methods

MRI experiments were performed on a 7T whole-body MR system (Siemens, Germany) using a custom-built dual-tuned 1H/23Na radiofrequency coil (diameter=27.9cm).

For simulation of the physiological compartments in the brain, a three-compartment phantom was fabricated with different agar gel concentrations (Fig.1). The method was tested in vivo on one human subject (male, 30years).

1H MRI: As a basis for brain masks as well as for anatomical comparison, MPRAGE sequence was performed (TR=2300ms, TE=2.86ms, resolution=1.25 mm isotropic, 1 average) with acquisition time (TA) of 5min. M0 maps of water content were calculated from 4 flip angles (1,4,8,10°) using spoiled gradient echo sequence (TR=8.6ms, TE=3.1ms, resolution=1.25mm isotropic, iPAT=2). Total TA was <6:30min.

23Na MRI: All sodium acquisitions were performed using a 15-pulse 3D non-Cartesian UTE FLORET sequence (Multi-FLORET)6,7 (Fig.1B). The i-pulses varied in flip angles (θi) and phases (φi,) with constat delay τi=5ms (Fig.1C) and duratio=1ms. Resolution was 5 mm isotropic, ADC duration was 4060ms with #interleaves/hub=818 (3 Hubs at 45°). Multi-FLORET in phantom: TR=620ms, TE=0.4ms, number of averages=2, TA=12:30 min/average. Multi-FLORET in brain: TR=470 ms, TE=0.4 ms, number of averages=1, TA=10:30 min/average.

Simulations: Multi-compartment signal was calculated with 16 irreducible spherical tensor operators in Matlab (MathWorks, USA). Parameters considered in the simulations include both sequence-specific parameters (θi, φi, τi, TE, TR), as well as compartment specific parameters in ranges: T1 [20-68]ms, T*2l [14-60]ms and T*2s [1-13]ms. As a measure of the apparent sodium concentrations we used magnetization in terms of: Mi=Ci x αi.

Results

Measurements of water fraction maps were in agreement with expected phantom water content (Fig.2A) and the method was then applied on the brain in vivo (Fig.2D). Representative evolution of the sodium signal after each of the 15 pulses of the acquisition in the phantom and in brain is depicted in Fig.3. Multi-compartment phantom filtering and quantification results from the phantom measurements are in Fig.4. The volume fractions from in vivo measurements were as follows: α1=0.58±0.09, α2=0.08±0.04 and α3=0.82±0.16. Estimated C1 was 10.87±9.74. Quantified maps of α1, α2, α3 and C1 from one volunteer are shown in Fig.5.

Discussion

The quantified phantom images of the magnetizations M1, M2, and M3 showed a good distinction between the phantom compartments, demonstrating the method’s applicability as a filtering technique for compartments with different relaxation times. According to theory, a distribution of α1~0.6, α2~0.2, and intracellular sodium concentration C1~0-20mM in gray and white matter brain tissue parts was expected. Our results show similar numbers in healthy brain.

Conclusions

The quantitative multi-compartment multi-pulse sodium MRI method presented in this preliminary study can be seen as a new approach to investigate intra- and extracellular sodium in vivo. We could differentiate brain compartments and provide an estimate of IC and EC sodium concentrations as well as IC, EC and CSF volume fractions.

Acknowledgements

The study was supported by the National Institutes of Health (NIH) grants: 1R01NS097494, 1R21CA213169 and 1P41EB017183.

References

1. G. Madelin and R. R. Regatte. Biomedical applications of sodium MRI in vivo. J Magn Reson Imaging, 38:511–529, 2013.
2. R. Ouwerkerk. Sodium MRI. Methods Mol Biol, 711:175–201, 2011.
3. P. M. Winter and N. Bansal. TmDOTP5 as a Na-23 shift reagent for the subcutaneously implanted 9L gliosarcoma in rats. Magn Reson Med, 45(3):436–442, 2001.
4. D. Ma, V. Gulani, N. Seiberlich, K. Liu, J. L. Sunshine, J. L. Duerk, and M. A. Griswold. Magnetic resonance fingerprinting. Nature, 495(7440):187–192, 2013.
5. M. Sabati, AA. Maudsley. Fast and high-resolution quantitative mapping of tissue water content with full brain coverage for clinically-driven studies. Magn Reson Imaging. 2013 Dec;31(10):1752-9
6. G. Madelin, R. Kline, R. Walvick, and R. R. Regatte. A method for estimating intracellular sodium concentration and extracellular volume fraction in brain in vivo using sodium magnetic resonance imaging. Sci Rep, 4:4763, 2014.
7. J.G. Pipe, N.R. Zwart, E.A. Aboussouan, R.K. Robison, A. Devaraj, and K.O. Johnson. A new design and rationale for 3D orthogonally oversampled k-space trajectories. Magn Reson Med, 66(5):1303–1311, 2011.

Figures

Figure 1: A - Cylindrical phantom with 140 mM sodium chloride (NaCl) in variably concentrated concentrically disposed agar gel compartments. B - (a) N-pulse FLORET sequence design with varying flip angles θi, phases φi, and time delays τi between i=1 to N RF pulses. C - Set of flip angles θi and phases φi optimized for the 15-pulse sequence as used in the present study in the phantom and in the brain.

Figure 2: Water content M0 maps. All maps were corrected for B1 inhomogeneity. A – Water content M0 map in 1.3mm isotropic resolution (axial slice) in the phantom. Signal was normalized to the mean signal of the central compartment. B – Cross-section of the map from A. C – Water fraction map downscaled to 5mm isotropic resolution to match sodium MRI data. D - Five representative axial slices of water content M0 map in 1.3mm isotropic resolution. Signal was normalized to CSF.

Figure 3: Time evolution of the maximum signal of different compartments in phantom and in brain after each RF pulse. (A-D): Comparison of simulated (blue) and measured (black) maximum magnitude sodium signals after each pulse of the Multi-FLORET sequence for agar and cerebrospinal fluid (CSF) in the brain. E – F: Absolute sodium signals over 15 pulses as simulated for three compartments in the brain: CSF, intracellular (IC), and extracellular (EC), before (E) and after (F) correction procedures (frequency, B1+).

Figure 4: Sodium MRI: Phantom: calculated volume fractions α1 (A), α2 (B) and α3 (C) and apparent total concentrations M1 (D), M2 (E) and M3 (F). According to the known sodium concentrations C1 = C2 = C3 = 140±5 mM all over the phantom. Mi=Ci x αi.

Figure 5: Sodium MRI: Brain - calculated volume fractions α1 (A), α2 (B), α3, (C) and C1 map (D).

Proc. Intl. Soc. Mag. Reson. Med. 26 (2018)
3876