Edited magnetic resonance spectroscopy in the neonatal brain

Yulu Song^{1

2}, Peter J Lally³, Maria Yanez Lopez⁴, Georg Oeltzschner^{1

2}, Mary Beth Nebel^{5

6}, Borjan Gagoski^{7

8}, Steven Kecskemeti⁹, Steve C N Hui^{1

2}, Helge J Zöllner^{1

2}, Deepika Shukla¹⁰, Tomoki Arichi^{4

11}, Enrico De Vita^{4

12}, Vivek Yedavalli¹³, Sudhin Thayyil¹⁰, Daniele Fallin^{14

15}, Douglas C Dean 3rd^{9

16

17}, P Ellen Grant^{7

8

18}, Jessica L Wisnowski^{19

20}, Richard A E Edden^{21

22

23}

Affiliations

¹ Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA.
³ Department of Brain Sciences, Imperial College London, London, UK.
⁴ Center for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.
⁵ Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, Baltimore, MD, 21205, USA.
⁶ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁷ Department of Radiology, Division of Neuroradiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
⁸ Fetal Neonatal Neuroimaging and Developmental Science Center, Boston Children's Hospital, Boston, MA, USA.
⁹ Waisman Center, University of WI-Madison, Madison, WI, 53705, USA.
¹⁰ Centre for Perinatal Neuroscience, Department of Brain Sciences, Imperial College London, London, UK.
¹¹ Department of Bioengineering, Imperial College London, South Kensington Campus, London, UK.
¹² Biomedical Engineering Department, School of Biomedical Engineering and Imaging Sciences, St Thomas's Hospital, Westminster Bridge Road, Lambeth Wing, 3rd Floor, London, SE1 7EH, UK.
¹³ Division of Neuroradiology, Park 367G, The Johns Hopkins University School of Medicine, 600 N. Wolfe St. B-112 D, Baltimore, MD, 21287, USA.
¹⁴ Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins University, Baltimore, USA.
¹⁵ Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, USA.
¹⁶ Department of Pediatrics, Division of Neonatology and Newborn Nursery, University of WI-Madison, School of Medicine and Public Health, Madison, WI, 53705, USA.
¹⁷ Department of Medical Physics, University of WI-Madison, School of Medicine and Public Health, Madison, WI, 53705, USA.
¹⁸ Department of Medicine, Division of Newborn Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
¹⁹ Children's Hospital Los Angeles, Los Angeles, CA, 90027, USA.
²⁰ Department of Radiology and Fetal and Neonatal Institute, CHLA Division of Neonatology, Department of Pediatrics, Children's Hospital of Los Angeles, University of Southern California, Los Angeles, CA, 90033, USA.
²¹ Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. raee2@jhu.edu.
²² F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA. raee2@jhu.edu.
²³ Division of Neuroradiology, Park 367G, The Johns Hopkins University School of Medicine, 600 N. Wolfe St. B-112 D, Baltimore, MD, 21287, USA. raee2@jhu.edu.

PMID: 34654960
PMCID: PMC8887832
DOI: 10.1007/s00234-021-02821-9

Review

Edited magnetic resonance spectroscopy in the neonatal brain

Yulu Song et al. Neuroradiology. 2022 Feb.

. 2022 Feb;64(2):217-232.

doi: 10.1007/s00234-021-02821-9. Epub 2021 Oct 15.

Authors

Affiliations

¹ Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA.
³ Department of Brain Sciences, Imperial College London, London, UK.
⁴ Center for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK.
⁵ Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, Baltimore, MD, 21205, USA.
⁶ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁷ Department of Radiology, Division of Neuroradiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
⁸ Fetal Neonatal Neuroimaging and Developmental Science Center, Boston Children's Hospital, Boston, MA, USA.
⁹ Waisman Center, University of WI-Madison, Madison, WI, 53705, USA.
¹⁰ Centre for Perinatal Neuroscience, Department of Brain Sciences, Imperial College London, London, UK.
¹¹ Department of Bioengineering, Imperial College London, South Kensington Campus, London, UK.
¹² Biomedical Engineering Department, School of Biomedical Engineering and Imaging Sciences, St Thomas's Hospital, Westminster Bridge Road, Lambeth Wing, 3rd Floor, London, SE1 7EH, UK.
¹³ Division of Neuroradiology, Park 367G, The Johns Hopkins University School of Medicine, 600 N. Wolfe St. B-112 D, Baltimore, MD, 21287, USA.
¹⁴ Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins University, Baltimore, USA.
¹⁵ Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, USA.
¹⁶ Department of Pediatrics, Division of Neonatology and Newborn Nursery, University of WI-Madison, School of Medicine and Public Health, Madison, WI, 53705, USA.
¹⁷ Department of Medical Physics, University of WI-Madison, School of Medicine and Public Health, Madison, WI, 53705, USA.
¹⁸ Department of Medicine, Division of Newborn Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
¹⁹ Children's Hospital Los Angeles, Los Angeles, CA, 90027, USA.
²⁰ Department of Radiology and Fetal and Neonatal Institute, CHLA Division of Neonatology, Department of Pediatrics, Children's Hospital of Los Angeles, University of Southern California, Los Angeles, CA, 90033, USA.
²¹ Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. raee2@jhu.edu.
²² F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA. raee2@jhu.edu.
²³ Division of Neuroradiology, Park 367G, The Johns Hopkins University School of Medicine, 600 N. Wolfe St. B-112 D, Baltimore, MD, 21287, USA. raee2@jhu.edu.

PMID: 34654960
PMCID: PMC8887832
DOI: 10.1007/s00234-021-02821-9

Abstract

J-difference-edited spectroscopy is a valuable approach for the detection of low-concentration metabolites with magnetic resonance spectroscopy (MRS). Currently, few edited MRS studies are performed in neonates due to suboptimal signal-to-noise ratio, relatively long acquisition times, and vulnerability to motion artifacts. Nonetheless, the technique presents an exciting opportunity in pediatric imaging research to study rapid maturational changes of neurotransmitter systems and other metabolic systems in early postnatal life. Studying these metabolic processes is vital to understanding the widespread and rapid structural and functional changes that occur in the first years of life. The overarching goal of this review is to provide an introduction to edited MRS for neonates, including the current state-of-the-art in editing methods and editable metabolites, as well as to review the current literature applying edited MRS to the neonatal brain. Existing challenges and future opportunities, including the lack of age-specific reference data, are also discussed.

Keywords: Edited MRS; J-difference editing; Low-concentration metabolites; Neonatal brain; Relaxation time.

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Conflict of interest statement

Conflict of interest The authors have no relevant financial or non-financial interests to disclose.

Figures

**Fig. 1**
Pathways relating the editable metabolites in the human brain. Abbreviations: TCA, tricarboxylic acid cycle; SSA, succinic semialdehyde; Asp, aspartate; Asc, ascorbate; GABA, γ-aminobutyric acid; NAA, N-acetylaspartate; NAAG, N-acetyl-aspartylglutamate

**Fig. 2**
Age-related change of the proton MRS brain spectra at 3 T. Infant (GA at birth, 36w; scanned at 38 weeks 6 days; volume = 24 × 40 × 24mm³ in bilateral thalamus, TE = 35 ms, average = 64), child (4-year-old, volume = 17 × 40 × 17mm³ in bilateral thalamus, TE = 35 ms, average = 32), adult (24-year-old, volume = 30 × 30 × 30mm³ in posterior cingulate, TE = 35 ms, average =64) short-TE PRESS spectra with TR = 2 s are shown, respectively. Spectra are normalized to the Cr signal amplitude. tCho, NAA, and Lac levels can be seen to change with age, as does the linewidth

**Fig. 3**
J-coupling. J-couplings of lactate (A) and GABA (B) are superimposed on the molecular structures as gray arrows. These result in the multiplet splittings seen in the simulated MR spectra below

**Fig. 4**
J-difference editing of GABA and lactate. GABA-edited spectra in simulation (A) and in vivo (B). The shaded region marks the edited GABA signal at 3 ppm. Lac-edited spectra in simulation (C) and in vivo (D). The shaded region marks the edited Lac signal at 1.3 ppm. Simulation sequence parameter: GABA: TE = 80 ms, field strength = 3 T; Lac: TE = 140 ms, field strength = 3 T. In vivo sequence parameter: GABA: TR = 2 s, TE = 80 ms, field strength = 3 T, averages = 320, acquisition bandwidth = 2000 Hz, acquisition time: 10 min 40 s; Lac: TR = 2 s, TE = 140 ms, field strength = 3 T, averages = 320, acquisition bandwidth = 2000 Hz, acquisition time: 10 min 40 s

**Fig. 5**
HERCULES-edited spectra in infant and child at 3 T. Infant (GA at birth, 36w; scanned at 38 weeks 6 days; volume = 17 × 40 × 17mm³ in bilateral thalamus, TE = 80 ms. Average = 56), child (4-year-old, volume = 24 × 40 × 24mm³ in bilateral thalamus, TE = 80 ms, average = 56) HERCULES spectra with TR = 2 s are shown, respectively. Spectra are normalized to the Cr signal amplitude. Y-scaling of difference spectra is increased by a factor of 4. Abbreviations: tCr, total creatine; tCho, total choline; mI, myo-inositol; Glx, glutamate + glutamine; tNAA, total N-acetyl aspartate; Lac, lactate; MM, macromolecule; GABA, γ-aminobutyric acid; Asc, ascorbate; PE, phosphorylethanolamine; GSH, glutathione; Asp, aspartate; NAAG, N-acetylaspartylglutamate

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References

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Edited magnetic resonance spectroscopy in the neonatal brain

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Edited magnetic resonance spectroscopy in the neonatal brain

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Conflict of interest statement

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