Please cite this article in press as: van de Looij, Y., et al., Advanced magnetic resonance spectroscopy and imaging techniques applied to brain development and animal models of perinatal injury. Int. J. Dev. Neurosci. (2015), http://dx.doi.org/10.1016/j.ijdevneu.2015.03.009 ARTICLE IN PRESS G Model DN-1976; No. of Pages 10 Int. J. Devl Neuroscience xxx (2015) xxx–xxx Contents lists available at ScienceDirect International Journal of Developmental Neuroscience j ourna l ho me page: www.elsevier.com/locate/ijdevneu Advanced magnetic resonance spectroscopy and imaging techniques applied to brain development and animal models of perinatal injury Yohan van de Looij a,b,* , Justin M. Dean c , Alistair J. Gunn c , Petra S. Hüppi a , Stéphane V. Sizonenko a a Division of Child Development & Growth, Department of Pediatrics, University of Geneva, Geneva, Switzerland b Laboratory for Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland c Department of Physiology, University of Auckland, Auckland, New Zealand a r t i c l e i n f o Article history: Received 5 February 2015 Received in revised form 25 March 2015 Accepted 25 March 2015 Available online xxx Keywords: Advanced magnetic resonance imaging Advanced magnetic resonance spectroscopy Animal models of perinatal brain injury Diffusion imaging Phase and susceptibility imaging Manganese enhanced magnetic resonance imaging a b s t r a c t Magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) are widely used in the field of brain development and perinatal brain injury. Due to technical progress the magnetic field strength (B 0 ) of MR systems has continuously increased, favoring 1 H-MRS with quantification of up to 18 metabolites in the brain and short echo time (TE) MRI sequences including phase and susceptibility imaging. For longer TE techniques including diffusion imaging modalities, the benefits of higher B 0 have not been clearly established. Nevertheless, progress has also been made in new advanced diffusion mod- els that have been developed to enhance the accuracy and specificity of the derived diffusion parameters. In this review, we will describe the latest developments in MRS and MRI techniques, including high-field 1 H-MRS, phase and susceptibility imaging, and diffusion imaging, and discuss their application in the study of cerebral development and perinatal brain injury. © 2015 Elsevier Ltd. All rights reserved. 1. Introduction Due to technical advances, the static magnetic field (B 0 ) of mag- netic resonance (MR) systems has continuously increased. Clinical Abbreviations: Mac, macromolecules; Asc, ascorbate; bhB, beta-hydroxibutirate; PCho, phosphorylcholine; Cr, creatine; PCr, phosphocreatine; GABA, -aminobuttyric acid; Glc, glucose; Glu, glutamate; Gln, glutamine; myo-Ins, myo- inositol; Lac, lactate; NAA, N-acetylaspartate; NAAG, N-acetylaspartylglutamate; PCr, phosphocreatine; PE, phosphoethanolamine; Tau, taurine; HI, hypoxia- Ischemia; LPS, lipopolysaccharide; MRI, magnetic resonance imaging; MRS, magnetic resonance spectroscopy; SNR, signal-to-noise ratio; TE, echo time; DTI, diffusion tensor imaging; QSM, quantitative susceptibility mapping; ADC, apparent diffusion coefficient; MD, mean diffusivity; D // , parallel diffusivity; D⊥, orthogonal diffusivity; FA, fractional anisotropy; NODDI, neurite orientation dispersion and density imaging; ficvf, intra-neurite volume fraction; fiso, cerebrospinal volume fraction; fia, intra-axonal volume fraction; ODI, orientation dispersion index; MEMRI, manganese enhanced magnetic resonance imaging; DKI, diffusion kurtosis imaging; MK, mean kurtosis; K // , parallel kurtosis; K⊥, orthogonal kurtosis; fMRI, functional magnetic resonance imaging. * Corresponding author at: Laboratory for Functional and Metabolic Imaging, EPFL-SB-IPSB-LIFMET, CH F1 602 – Station 6, 1015 Lausanne, Switzerland. Tel.: +41 21 693 79 38; fax: +41 21 693 79 60. E-mail address: yohan.vandelooij@epfl.ch (Y. van de Looij). state-of-the-art scanners reach 3.0 T, although 7.0 T and 9.4 T are also available for clinical research, while animal scanners range from 3.0 T to 21.0 T, including 4.7 T, 7.0 T, 9.4 T, 11.7 T, 14.1 T and 17.0 T. This drive for increasing B 0 relates to the almost linear increase in the signal-to-noise ratio (SNR) with B 0 , due to an almost linear increase of magnetization of the sample (Callaghan, 1991). This increase in SNR provides increased image resolution and reduced scanning time (i.e., “better and faster”). An increase in the spectral resolution with B 0 is particularly advantageous for MR techniques such as MR spectroscopy (MRS). The recent development of advanced localized 1 H magnetic reso- nance spectroscopy ( 1 H-MRS) at high magnetic fields (e.g., ≥7.0 T) has allowed quantification of concentrations of up to 18 metabo- lites in the rodent brain (termed the “neurochemical profile”), including antioxidants, compounds related to energy metabolism, neurotransmission, membrane precursor, osmoregulation, myeli- nation, neuronal markers, glial markers, and neuroprotection (Lei et al., 2009; Mlynarik et al., 2008, 2006; Tkac et al., 2003; van de Looij et al., 2011). 1 H-MRS has also been used to follow the changes in the neurochemical profile during rat brain development and maturation (Tkac et al., 2003). Further, cerebral hypoxia-ischemia (HI) or inflammation leads to specific changes in the neurochemi- http://dx.doi.org/10.1016/j.ijdevneu.2015.03.009 0736-5748/© 2015 Elsevier Ltd. All rights reserved.