Kylie Yeung1,2,3, Jordan McGing1, Aaron Axford1, Sarah Birkhoelzer1, Ayaka Shinozaki1,4, Andrew Lewis1, Jenny Rayner1, Oliver Rider1, Rolf Schulte5, Fergus Gleeson2,3, Damian Tyler1,4, and James Grist1,3,4,6
1Oxford Centre for Clinical Magnetic Resonance Research (OCMR), University of Oxford, Oxford, United Kingdom, 2Department of Oncology, University of Oxford, Oxford, United Kingdom, 3Department of Radiology, Oxford University Hospitals, Oxford, United Kingdom, 4Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom, 5GE HealthCare, Munich, Germany, 6Alma Mater Studorium, University of Bologna, Bologna, Italy
Synopsis
Keywords: Hyperpolarized MR (Non-Gas), Hyperpolarized MR (Non-Gas), B1 correction, B0 correction
Motivation: B0 and B1 inhomogeneities affect signal quantification and kinetic modelling but are challenging to map and correct for in hyperpolarized MRI due to the signal being exogenous and non-renewable.
Goal(s): Develop a fully-integrated B0 and B1 mapping method that does not require specialized pulse sequence programming, additional hardware, nor any additional carbon-13 dose.
Approach: Varying echo times and flip angles in the imaging sequence.
Results: The in-vivo field maps agreed well with independently acquired maps and could correct for B0 off-resonance blurring and B1 inhomogeneity.
Impact: A fully-integrated B0 and B1 mapping and
correction method for hyperpolarized carbon-13 MRI is presented and validated
in vivo. This method is readily implemented and can improve image quality,
helping 13C metabolic imaging become more robust for clinical
studies.
Introduction
Hyperpolarized carbon-13 metabolic imaging is
an emerging technique whereby metabolic processes can be probed by imaging
carbon-13 labelled molecules and their conversion into downstream metabolites [1,2], enabling the early monitoring of various diseases before
detectable structural changes [3-5].
Correcting for field inhomogeneities in
hyperpolarized MRI has been a challenge due to the exogenous and non-renewable nature
of the hyperpolarized signal. Currently, few B0 and B1 mapping methods for
hyperpolarized MRI carbon-13 MRI exist that do not require additional coils or
phantoms [6,7], specialized pulse sequence programming software [8], or the administration of an additional hyperpolarized carbon-13
dose. This means that coil-induced inhomogeneities and off-resonance blurring
artifacts are often not adequately corrected for, affecting signal
quantification and kinetic modelling [9,10].
We propose a simple method to integrate B0 and
B1 mapping into a hyperpolarized carbon-13 imaging sequence, using varied flip
angle (FA) and varied echo time (TE) repetitions of a standard pulse sequence. We
validate, in 2 human brain scans, the acquisition of inherently co-registered
B0 and B1 maps within the imaging sequence. Furthermore, we demonstrate using
the acquired field maps to correct for inhomogeneities and off-resonance blurring.Methods
The study was conducted after local ethical
approval and written informed consent from participants. Images were acquired on
a 3T GE Premier (GE Healthcare, WI) using a dual-tuned 1H/13C
birdcage head coil (Rapid Biomedical, Germany). Two healthy volunteers (male;
age 64 and 67) were scanned after intravenous injection of 0.4ml/kg of 250mM
hyperpolarized sodium [1-13C]pyruvate following polarization for ~4hours in a SPINLab hyperpolarizer (GE Healthcare, WI) [11]. Transmit gain (TG) for 13C was calibrated using a
thermal 13C urea phantom placed by the participant’s head.
The imaging protocol used a
spectral-spatial multi-slice single-arm spiral sequence (16x16 acquisition matrix, 240x240mm FOV, eight 20mm slices, 32x32
reconstruction matrix) [12] with pyruvate (FApy:5o), lactate
(FAlac:15o), and bicarbonate (FAbic:60o)
maps acquired at ~4s intervals.
Variable TE acquisitions (2, 3, and 5 milliseconds) at the pyruvate frequency were interleaved ~20s after injection using low flip angles (5o) (Fig. 1). The B0 map was
obtained by fitting the signal phase using the MEDI toolbox [13-15], and evaluated against a standard proton B0 map acquired using the
same coil.
Variable FA acquisitions
(40o, 50o, and 60o) at the pyruvate frequency were interleaved ~45s
after injection for B1 mapping. The signal was fitted voxel-wise to the
following equation:
$$S=M_0{\cdot}exp\left(-\frac{TR}{T_1}\right)^{TR{\cdot}Time_t}{\cdot}sin(\Delta{B_1}{\cdot}FA_{Time})\prod_{Time_0}^{Time_t}cos(\Delta{B_1}{\cdot}FA_{Time})$$
where S is the signal, M0 is initial magnetization, TR is repetition time, FA is flip angle, Time is a vector of time points during acquisition, and ΔB1 is transmit B1 variation.
The in vivo B1 map was evaluated against a separately acquired B1 Map using a spherical silicone-oil phantom (2D CSI, 1.4ms partial self-refocused pulse, 16x16 acquisition matrix, 240x240mm FOV, 8.3s TR, FAs=40,60,80,90,100,120,160o, signals fitted voxel-wise to $$$S=M_0{\cdot}sin(\Delta B_1{\cdot}FA_{Time})$$$).
Image correction was performed after smoothing of both field maps using polynomial fitting and extrapolation (second order, kernel width = 4) [16]. Multi-frequency interpolation (MFI) was used for B0 correction [17,18]. Prior to B1 correction, metabolite maps were divided by $$$sin(FA_{metabolite})$$$. Assuming transmit-receive reciprocity, B1 correction was then performed:
$$I'_{metabolite}=I{\cdot}\frac{sin(FA_{metabolite})}{sin(\Delta{B_1}{\cdot}FA_{metabolite})}{\cdot}\frac{1}{\Delta{B_1}}$$
Where I’ is corrected image and I is measured image.Results
B0 maps from 13C imaging sequence match well with proton B0 maps (standard deviations: 14.04 Hz from 13C and 17.78 Hz from 1H (Participant 1); 22.43 Hz from 13C and 26.78 Hz from 1H (Participant 2)) (Fig. 2). Applying MFI shows deblurring in the metabolite maps (Fig. 3). In vivo 13C ΔB1 maps (mean ΔB1 ± SD: 0.98±0.11 (Participant 1); 0.92±0.12 (Participant 2)) show good agreement with the phantom B1 Map (Fig. 4). B1 correction increases signal intensity towards the coil center (Fig. 5). The average signal change is -0.14%±3.77%. Discussion
This study validated a fully-integrated B0 and B1 mapping method which is more straightforward to implement than existing
methods, only requiring altering the parameters FA, TE, and TR of a standard
pulse sequence. The acquired maps are inherently co-registered and patient-specific.
The B0 map was acquired roughly around the
middle of the bolus to maximize SNR and the B1 map was acquired with high
flip-angles at the end of pyruvate bolus to effectively use up residual
magnetization. Field homogeneities are assumed to be similar for all
metabolites of interest.Conclusion
A B0 and B1 mapping method which is fully
integrated into the carbon-13 imaging sequence is presented and validated in
vivo for two human brains, and shows good agreement with independently acquired
field maps. B0 and B1 correction shows sharpened images and improved signal
homogeneity.Acknowledgements
This work was supported by the John Fell Fund. Acknowledgement must also be given to Oxford-MRC Doctoral Training Partnership iCASE award, the Oxford-Radcliffe Scholarship, and GE HealthCare for funding this project.References
[1] M.
Vaeggemose, R. F. Schulte, and C. Laustsen, ‘Comprehensive Literature Review of
Hyperpolarized Carbon-13 MRI: The Road to Clinical Application’, Metabolites,
vol. 11, no. 4, p. 219, Apr. 2021, doi: 10.3390/metabo11040219.
[2] P. E. Z. Larson and J. W. Gordon,
‘Hyperpolarized Metabolic MRI—Acquisition, Reconstruction, and Analysis
Methods’, Metabolites, vol. 11, no. 6, Art. no. 6, Jun. 2021, doi:
10.3390/metabo11060386.
[3] M. A. Schroeder, L. E. Cochlin, L. C.
Heather, K. Clarke, G. K. Radda, and D. J. Tyler, ‘In vivo assessment of
pyruvate dehydrogenase flux in the heart using hyperpolarized carbon-13
magnetic resonance’, Proc. Natl. Acad. Sci., vol. 105, no. 33, pp.
12051–12056, Aug. 2008, doi: 10.1073/pnas.0805953105.
[4] Z. Ye, B. Song, P. M. Lee, M. A.
Ohliger, and C. Laustsen, ‘Hyperpolarized carbon 13 MRI in liver diseases:
Recent advances and future opportunities’, Liver Int., vol. 42, no. 5,
pp. 973–983, May 2022, doi: 10.1111/liv.15222.
[5] R. Woitek et al.,
‘Hyperpolarized Carbon-13 MRI for Early Response Assessment of Neoadjuvant
Chemotherapy in Breast Cancer Patients’, Cancer Res., vol. 81, no. 23,
pp. 6004–6017, Dec. 2021, doi: 10.1158/0008-5472.CAN-21-1499.
[6] I. Park et al., ‘Development of
methods and feasibility of using hyperpolarized carbon-13 imaging data for
evaluating brain metabolism in patient studies’, Magn. Reson. Med., vol.
80, no. 3, pp. 864–873, 2018, doi: 10.1002/mrm.27077.
[7] P. M. Lee et al., ‘Whole-Abdomen
Metabolic Imaging of Healthy Volunteers Using Hyperpolarized [1-13C]pyruvate
MRI’, J. Magn. Reson. Imaging, vol. 56, no. 6, pp. 1792–1806, 2022, doi:
10.1002/jmri.28196.
[8] S. Tang et al., ‘A regional
bolus tracking and real-time B1 calibration method for hyperpolarized 13C MRI’,
Magn. Reson. Med., vol. 81, no. 2, pp. 839–851, 2019, doi:
10.1002/mrm.27391.
[9] D. Mammoli et al., ‘Kinetic
Modeling of Hyperpolarized Carbon-13 Pyruvate Metabolism in the Human Brain’, IEEE
Trans. Med. Imaging, vol. 39, no. 2, pp. 320–327, Feb. 2020, doi:
10.1109/TMI.2019.2926437.
[10] B. T. Chung et al.,
‘Hyperpolarized [2–13C]pyruvate MR molecular imaging with whole brain
coverage’, NeuroImage, vol. 280, p. 120350, Oct. 2023, doi:
10.1016/j.neuroimage.2023.120350.
[11] J. T. Grist et al., ‘Quantifying
normal human brain metabolism using hyperpolarized [1–13C]pyruvate and magnetic
resonance imaging’, NeuroImage, vol. 189, pp. 171–179, Apr. 2019, doi:
10.1016/j.neuroimage.2019.01.027.
[12] R. F. Schulte et al.,
‘Saturation-recovery metabolic-exchange rate imaging with hyperpolarized
[1-13C] pyruvate using spectral-spatial excitation’, Magn. Reson. Med.,
vol. 69, no. 5, pp. 1209–1216, 2013, doi: 10.1002/mrm.24353.
[13] T. Liu, C. Wisnieff, M. Lou, W. Chen, P.
Spincemaille, and Y. Wang, ‘Nonlinear formulation of the magnetic field to
source relationship for robust quantitative susceptibility mapping’, Magn.
Reson. Med., vol. 69, no. 2, pp. 467–476, 2013, doi: 10.1002/mrm.24272.
[14] B. Kressler, L. de Rochefort, T. Liu, P.
Spincemaille, Q. Jiang, and Y. Wang, ‘Nonlinear Regularization for Per Voxel
Estimation of Magnetic Susceptibility Distributions From MRI Field Maps’, IEEE
Trans. Med. Imaging, vol. 29, no. 2, pp. 273–281, Feb. 2010, doi:
10.1109/TMI.2009.2023787.
[15] L. de Rochefort, R. Brown, M. R. Prince,
and Y. Wang, ‘Quantitative MR susceptibility mapping using piece-wise constant
regularized inversion of the magnetic field’, Magn. Reson. Med., vol.
60, no. 4, pp. 1003–1009, 2008, doi: 10.1002/mrm.21710.
[16] K. P. Pruessmann, M. Weiger, M. B.
Scheidegger, and P. Boesiger, ‘SENSE: Sensitivity encoding for fast MRI’, Magn.
Reson. Med., vol. 42, no. 5, pp. 952–962, 1999, doi: 10.1002/(SICI)1522-2594(199911)42:5<952::AID-MRM16>3.0.CO;2-S.
[17] L.-C. Man, J. M. Pauly, and A. Macovski,
‘Multifrequency interpolation for fast off-resonance correction’, Magn.
Reson. Med., vol. 37, no. 5, pp. 785–792, 1997, doi:
10.1002/mrm.1910370523.
[18] A. Nylund, ‘Off-resonance correction for
magnetic resonance imaging with spiral trajectories’, Bachelor of Science
Thesis, KTH Royal Institute of Technology, Sweden, 2014. Accessed: Nov. 01,
2023. [Online]. Available: https://www.semanticscholar.org/paper/Off-resonance-correction-for-magnetic-resonance-Nylund/f2986a42d2bc22aa58ab0a555a5268e8c7b0dc2b