Advanced Techniques and Applications in Magnetic Resonance Spectroscopy for Pediatric Patients

Abstract

Magnetic resonance spectroscopy (MRS) is a noninvasive tool that is often used in conjunction with conventional MR imaging to acquire information regarding the biochemistry of tissue. In pediatric patients, the traditional clinical application of MRS was in the preoperative diagnostic workup of brain tumors. In recent years with the boom of molecular testing, MRS application for tumor evaluation is becoming more advanced, now potentially serving as a biomarker for molecular subgroup classification. This article will review MRS techniques as well as clinical applications, both conventional and more advanced applications in the pediatric population including tumor assessment, hypoxic-ischemic injury, abusive head injury, and autism.

Keywords

MR spectroscopy - pediatric brain tumors - hypoxic-ischemic encephalopathy - abusive head injury - autism

• References

• 1 Martín Noguerol T, Sánchez-González J, Martínez Barbero JP, García-Figueiras R, Baleato-González S, Luna A. Clinical imaging of tumor metabolism with ¹H-magnetic resonance spectroscopy. Magn Reson Imaging Clin N Am 2016; 24 (01) 57-86
• 2 Astrakas LG, Argyropoulou MI. Key concepts in MR spectroscopy and practical approaches to gaining biochemical information in children. Pediatr Radiol 2016; 46 (07) 941-951
• 3 Schneider JF. MR spectroscopy in children: protocols and pitfalls in non-tumorous brain pathology. Pediatr Radiol 2016; 46 (07) 963-982
• 4 Zarifi M, Tzika AA. Proton MRS imaging in pediatric brain tumors. Pediatr Radiol 2016; 46 (07) 952-962
• 5 Nelson SJ, Vigneron DB, Dillon WP. Serial evaluation of patients with brain tumors using volume MRI and 3D 1H MRSI. NMR Biomed 1999; 12 (03) 123-138
• 6 Graves EE, Nelson SJ, Vigneron DB. , et al. A preliminary study of the prognostic value of proton magnetic resonance spectroscopic imaging in gamma knife radiosurgery of recurrent malignant gliomas. Neurosurgery 2000; 46 (02) 319-326 , discussion 326–328
• 7 Graves EE, Nelson SJ, Vigneron DB. , et al. Serial proton MR spectroscopic imaging of recurrent malignant gliomas after gamma knife radiosurgery. Am J Neuroradiol 2001; 22 (04) 613-624
• 8 Tzika AA, Cheng LL, Goumnerova L. , et al. Biochemical characterization of pediatric brain tumors by using in vivo and ex vivo magnetic resonance spectroscopy. J Neurosurg 2002; 96 (06) 1023-1031
• 9 Panigrahy A, Nelson Jr MD, Blüml S. Magnetic resonance spectroscopy in pediatric neuroradiology: clinical and research applications. Pediatr Radiol 2010; 40 (01) 3-30
• 10 Otsuki T, Kanamatsu T, Tsukada Y, Goto Y, Okamoto K, Watanabe H. Carbon 13-labeled magnetic resonance spectroscopy observation of cerebral glucose metabolism: metabolism in MELAS: case report. Arch Neurol 2005; 62 (03) 485-487
• 11 Warburg O. On the origin of cancer cells. Science 1956; 123 (3191): 309-314
• 12 Park I, Larson PEZ, Zierhut ML. , et al. Hyperpolarized 13C magnetic resonance metabolic imaging: application to brain tumors. Neuro-oncol 2010; 12 (02) 133-144
• 13 Gutte H, Hansen AE, Johannesen HH. , et al. The use of dynamic nuclear polarization (13)C-pyruvate MRS in cancer. Am J Nucl Med Mol Imaging 2015; 5 (05) 548-560
• 14 Kaibara T, Tyson RL, Sutherland GR. Human cerebral neoplasms studied using MR spectroscopy: a review. Biochem Cell Biol 1998; 76 (2-3): 477-486
• 15 Herholz K, Heindel W, Luyten PR. , et al. In vivo imaging of glucose consumption and lactate concentration in human gliomas. Ann Neurol 1992; 31 (03) 319-327
• 16 Terpstra M, Gruetter R, High WB. , et al. Lactate turnover in rat glioma measured by in vivo nuclear magnetic resonance spectroscopy. Cancer Res 1998; 58 (22) 5083-5088
• 17 Ziegler A, von Kienlin M, Décorps M, Rémy C. High glycolytic activity in rat glioma demonstrated in vivo by correlation peak 1H magnetic resonance imaging. Cancer Res 2001; 61 (14) 5595-5600
• 18 Li Y, Park I, Nelson SJ. Imaging tumor metabolism using in vivo magnetic resonance spectroscopy. Cancer J 2015; 21 (02) 123-128
• 19 Chaumeil MM, Larson PEZ, Woods SM. , et al. Hyperpolarized [1-13C] glutamate: a metabolic imaging biomarker of IDH1 mutational status in glioma. Cancer Res 2014; 74 (16) 4247-4257
• 20 Ren J, Sherry AD, Malloy CR. (31)P-MRS of healthy human brain: ATP synthesis, metabolite concentrations, pH, and T1 relaxation times. NMR Biomed 2015; 28 (11) 1455-1462
• 21 Dewhirst MW, Sostman HD, Leopold KA. , et al. Soft-tissue sarcomas: MR imaging and MR spectroscopy for prognosis and therapy monitoring. Work in progress. Radiology 1990; 174 (3 Pt 1): 847-853
• 22 Griffiths JR, Cady E, Edwards RH, McCready VR, Wilkie DR, Wiltshaw E. 31P-NMR studies of a human tumour in situ. Lancet 1983; 1 (8339): 1435-1436
• 23 Miyamachi K, Abe H, Miyasaka K. Phosphorus-31 MR spectroscopy of brain tumors [in Japanese]. No Shinkei Geka 1990; 18 (06) 533-537
• 24 Ordys BB, Launay S, Deighton RF, McCulloch J, Whittle IR. The role of mitochondria in glioma pathophysiology. Mol Neurobiol 2010; 42 (01) 64-75
• 25 Poussaint TY. Magnetic resonance imaging of pediatric brain tumors: state of the art. Top Magn Reson Imaging 2001; 12 (06) 411-433
• 26 Yeom KW, Mitchell LA, Lober RM. , et al. Arterial spin-labeled perfusion of pediatric brain tumors. Am J Neuroradiol 2014; 35 (02) 395-401
• 27 Panigrahy A, Blüml S. Neuroimaging of pediatric brain tumors: from basic to advanced magnetic resonance imaging (MRI). J Child Neurol 2009; 24 (11) 1343-1365
• 28 Lequin M, Hendrikse J. Advanced MR imaging in pediatric brain tumors, clinical applications. Neuroimaging Clin N Am 2017; 27 (01) 167-190
• 29 Blüml S, Panigrahy A, Laskov M. , et al. Elevated citrate in pediatric astrocytomas with malignant progression. Neuro-oncol 2011; 13 (10) 1107-1117
• 30 Smith EA, Carlos RC, Junck LR, Tsien CI, Elias A, Sundgren PC. Developing a clinical decision model: MR spectroscopy to differentiate between recurrent tumor and radiation change in patients with new contrast-enhancing lesions. Am J Roentgenol 2009; 192 (02) W45-52
• 31 Elias AE, Carlos RC, Smith EA. , et al. MR spectroscopy using normalized and non-normalized metabolite ratios for differentiating recurrent brain tumor from radiation injury. Acad Radiol 2011; 18 (09) 1101-1108
• 32 Laprie A, Pirzkall A, Haas-Kogan DA. , et al. Longitudinal multivoxel MR spectroscopy study of pediatric diffuse brainstem gliomas treated with radiotherapy. Int J Radiat Oncol Biol Phys 2005; 62 (01) 20-31
• 33 Zinn PO, Mahmood Z, Elbanan MG, Colen RR. Imaging genomics in gliomas. Cancer J 2015; 21 (03) 225-234
• 34 Blüml S, Margol AS, Sposto R. , et al. Molecular subgroups of medulloblastoma identification using noninvasive magnetic resonance spectroscopy. Neuro-oncol 2016; 18 (01) 126-131
• 35 Ichimura K, Nishikawa R, Matsutani M. Molecular markers in pediatric neuro-oncology. Neuro-oncol 2012; 14 (Suppl. 04) iv90-iv99
• 36 Astrakas L, Blekas KD, Constantinou C. , et al. Combining magnetic resonance spectroscopy and molecular genomics offers better accuracy in brain tumor typing and prediction of survival than either methodology alone. Int J Oncol 2011; 38 (04) 1113-1127
• 37 Tzika AA, Astrakas LG, Zarifi MK. , et al. Spectroscopic and perfusion magnetic resonance imaging predictors of progression in pediatric brain tumors. Cancer 2004; 100 (06) 1246-1256
• 38 Astrakas L, Zurakowski D, Marcus KJ. , et al. Proton MRSI biomarkers predict survival in children with CNS tumors. In: Miami, FL: International Society for Magnetic Resonance in Medicine; 2005: 145
• 39 Marcus KJ, Astrakas LG, Zurakowski D. , et al. Predicting survival of children with CNS tumors using proton magnetic resonance spectroscopic imaging biomarkers. Int J Oncol 2007; 30 (03) 651-657
• 40 Pomeroy SL, Tamayo P, Gaasenbeek M. , et al. Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature 2002; 415 (6870): 436-442
• 41 Nutt CL, Mani DR, Betensky RA. , et al. Gene expression-based classification of malignant gliomas correlates better with survival than histological classification. Cancer Res 2003; 63 (07) 1602-1607
• 42 Babourina-Brooks B, Wilson M, Arvanitis TN, Peet AC, Davies NP. MRS water resonance frequency in childhood brain tumours: a novel potential biomarker of temperature and tumour environment. NMR Biomed 2014; 27 (10) 1222-1229
• 43 Kateb B, Yamamoto V, Yu C, Grundfest W, Gruen JP. Infrared thermal imaging: a review of the literature and case report. Neuroimage 2009; 47 (Suppl. 02) T154-T162
• 44 Gerweck LE, Seetharaman K. Cellular pH gradient in tumor versus normal for the treatment of cancer. Cancer Res 1996; 56 (06) 1194-1198
• 45 Kim H, Kim S, Lee HH, Heo H. In-vivo magnetic resonance spectroscopy of 2-hydroxyglutarate in isocitrate dehydrogenase-mutated gliomas: a technical review for neuroradiologists. Korean J Radiol 2016; 17 (05) 620-632
• 46 Buccoliero AM, Castiglione F, Degl'Innocenti DR, Gheri CF, Genitori L, Taddei GL. IDH1 mutation in pediatric gliomas: has it a diagnostic and prognostic value?. Fetal Pediatr Pathol 2012; 31 (05) 278-282
• 47 Nelson KB, Leviton A. How much of neonatal encephalopathy is due to birth asphyxia?. Am J Dis Child 1991; 145 (11) 1325-1331
• 48 Finer NN, Robertson CM, Richards RT, Pinnell LE, Peters KL. Hypoxic-ischemic encephalopathy in term neonates: perinatal factors and outcome. J Pediatr 1981; 98 (01) 112-117
• 49 Zhu W, Zhong W, Qi J, Yin P, Wang C, Chang L. Proton magnetic resonance spectroscopy in neonates with hypoxic-ischemic injury and its prognostic value. Transl Res 2008; 152 (05) 225-232
• 50 Malik GK, Pandey M, Kumar R, Chawla S, Rathi B, Gupta RK. MR imaging and in vivo proton spectroscopy of the brain in neonates with hypoxic ischemic encephalopathy. Eur J Radiol 2002; 43 (01) 6-13
• 51 Robertson NJ, Wyatt JS. The magnetic resonance revolution in brain imaging: impact on neonatal intensive care. Arch Dis Child Fetal Neonatal Ed 2004; 89 (03) F193-F197
• 52 da Silva LF, Höefel Filho JR, Anés M, Nunes ML. Prognostic value of 1H-MRS in neonatal encephalopathy. Pediatr Neurol 2006; 34 (05) 360-366
• 53 Frankenburg WK, Dodds J, Archer P, Shapiro H, Bresnick B. The Denver II: a major revision and restandardization of the Denver Developmental Screening Test. Pediatrics 1992; 89 (01) 91-97
• 54 Novotny E, Ashwal S, Shevell M. Proton magnetic resonance spectroscopy: an emerging technology in pediatric neurology research. Pediatr Res 1998; 44 (01) 1-10
• 55 Wang Z, Zimmerman RA, Sauter R. Proton MR spectroscopy of the brain: clinically useful information obtained in assessing CNS diseases in children. Am J Roentgenol 1996; 167 (01) 191-199
• 56 Gluckman PD, Wyatt JS, Azzopardi D. , et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 2005; 365 (9460): 663-670
• 57 Shankaran S, Laptook AR, Ehrenkranz RA. , et al; National Institute of Child Health and Human Development Neonatal Research Network. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005; 353 (15) 1574-1584
• 58 Azzopardi DV, Strohm B, Edwards AD. , et al; TOBY Study Group. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med 2009; 361 (14) 1349-1358
• 59 Edwards AD, Brocklehurst P, Gunn AJ. , et al. Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data. BMJ 2010; 340: c363
• 60 Thakur NH, Spencer AJ, Kilbride HW, Lowe LH. Findings and patterns on MRI and MR spectroscopy in neonates after therapeutic hypothermia for hypoxic ischemic encephalopathy treatment. South Med J 2013; 106 (06) 350-355
• 61 Zanelli S, Buck M, Fairchild K. Physiologic and pharmacologic considerations for hypothermia therapy in neonates. J Perinatol 2011; 31 (06) 377-386
• 62 Wintermark P, Hansen A, Soul J, Labrecque M, Robertson RL, Warfield SK. Early versus late MRI in asphyxiated newborns treated with hypothermia. Arch Dis Child Fetal Neonatal Ed 2011; 96 (01) F36-F44
• 63 Wisnowski JL, Wu TW, Reitman AJ. , et al. The effects of therapeutic hypothermia on cerebral metabolism in neonates with hypoxic-ischemic encephalopathy: An in vivo 1H-MR spectroscopy study. J Cereb Blood Flow Metab 2016; 36 (06) 1075-1086
• 64 Mellergård P, Nordström CH. Intracerebral temperature in neurosurgical patients. Neurosurgery 1991; 28 (05) 709-713
• 65 Karaszewski B, Wardlaw JM, Marshall I. , et al. Early brain temperature elevation and anaerobic metabolism in human acute ischaemic stroke. Brain 2009; 132 (Pt 4): 955-964
• 66 Schwab S, Spranger M, Aschoff A, Steiner T, Hacke W. Brain temperature monitoring and modulation in patients with severe MCA infarction. Neurology 1997; 48 (03) 762-767
• 67 Laptook A, Tyson J, Shankaran S. , et al; National Institute of Child Health and Human Development Neonatal Research Network. Elevated temperature after hypoxic-ischemic encephalopathy: risk factor for adverse outcomes. Pediatrics 2008; 122 (03) 491-499
• 68 Wu TW, McLean C, Friedlich P. , et al. Brain temperature in neonates with hypoxic-ischemic encephalopathy during therapeutic hypothermia. J Pediatr 2014; 165 (06) 1129-1134
• 69 Jørgensen HS, Reith J, Pedersen PM, Nakayama H, Olsen TS. Body temperature and outcome in stroke patients. Lancet 1996; 348 (9021): 193
• 70 Reith J, Jørgensen HS, Pedersen PM. , et al. Body temperature in acute stroke: relation to stroke severity, infarct size, mortality, and outcome. Lancet 1996; 347 (8999): 422-425
• 71 Lescohier I, DiScala C. Blunt trauma in children: causes and outcomes of head versus extracranial injury. Pediatrics 1993; 91 (04) 721-725
• 72 Makoroff KL, Cecil KM, Care M, Ball Jr WS. Elevated lactate as an early marker of brain injury in inflicted traumatic brain injury. Pediatr Radiol 2005; 35 (07) 668-676
• 73 Condon B, Oluoch-Olunya D, Hadley D, Teasdale G, Wagstaff A. Early 1H magnetic resonance spectroscopy of acute head injury: four cases. J Neurotrauma 1998; 15 (08) 563-571
• 74 Haseler LJ, Arcinue E, Danielsen ER, Bluml S, Ross BD. Evidence from proton magnetic resonance spectroscopy for a metabolic cascade of neuronal damage in shaken baby syndrome. Pediatrics 1997; 99 (01) 4-14
• 75 Holshouser BA, Ashwal S, Luh GY. , et al. Proton MR spectroscopy after acute central nervous system injury: outcome prediction in neonates, infants, and children. Radiology 1997; 202 (02) 487-496
• 76 Holshouser BA, Ashwal S, Shu S, Hinshaw Jr DB. Proton MR spectroscopy in children with acute brain injury: comparison of short and long echo time acquisitions. J Magn Reson Imaging 2000; 11 (01) 9-19
• 77 Ross BD, Ernst T, Kreis R. , et al. 1H MRS in acute traumatic brain injury. J Magn Reson Imaging 1998; 8 (04) 829-840
• 78 Choe BY, Suh TS, Choi KH, Shinn KS, Park CK, Kang JK. Neuronal dysfunction in patients with closed head injury evaluated by in vivo 1H magnetic resonance spectroscopy. Invest Radiol 1995; 30 (08) 502-506
• 79 Sutton LN, Wang Z, Duhaime AC, Costarino D, Sauter R, Zimmerman R. Tissue lactate in pediatric head trauma: a clinical study using 1H NMR spectroscopy. Pediatr Neurosurg 1995; 22 (02) 81-87
• 80 Cecil KM, Hills EC, Sandel ME. , et al. Proton magnetic resonance spectroscopy for detection of axonal injury in the splenium of the corpus callosum of brain-injured patients. J Neurosurg 1998; 88 (05) 795-801
• 81 Ashwal S, Holshouser BA, Shu SK. , et al. Predictive value of proton magnetic resonance spectroscopy in pediatric closed head injury. Pediatr Neurol 2000; 23 (02) 114-125
• 82 Jope RS, Jenden DJ. Choline and phospholipid metabolism and the synthesis of acetylcholine in rat brain. J Neurosci Res 1979; 4 (01) 69-82
• 83 Miller BL. A review of chemical issues in 1H NMR spectroscopy: N-acetyl-L-aspartate, creatine and choline. NMR Biomed 1991; 4 (02) 47-52
• 84 Pfefferbaum A, Adalsteinsson E, Spielman D, Sullivan EV, Lim KO. In vivo spectroscopic quantification of the N-acetyl moiety, creatine, and choline from large volumes of brain gray and white matter: effects of normal aging. Magn Reson Med 1999; 41 (02) 276-284
• 85 Badar-Goffer RS, Ben-Yoseph O, Bachelard HS, Morris PG. Neuronal-glial metabolism under depolarizing conditions. A 13C-n.m.r. study. Biochem J 1992; 282 (Pt 1): 225-230
• 86 Brand A, Richter-Landsberg C, Leibfritz D. Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. Dev Neurosci 1993; 15 (3-5): 289-298
• 87 Ford TC, Crewther DP. A comprehensive review of the ¹H-MRS metabolite spectrum in autism spectrum disorder. Front Mol Neurosci 2016; 9: 14
• 88 Chugani DC. Neuroimaging and neurochemistry of autism. Pediatr Clin North Am 2012; 59 (01) 63-73 , x
• 89 Joshi G, Biederman J, Wozniak J. , et al. Magnetic resonance spectroscopy study of the glutamatergic system in adolescent males with high-functioning autistic disorder: a pilot study at 4T. Eur Arch Psychiatry Clin Neurosci 2013; 263 (05) 379-384
• 90 Doyle-Thomas KA, Card D, Soorya LV, Wang AT, Fan J, Anagnostou E. Metabolic mapping of deep brain structures and associations with symptomatology in autism spectrum disorders. Res Autism Spectr Disord 2014; 8 (01) 44-51
• 91 Rae CD. A guide to the metabolic pathways and function of metabolites observed in human brain 1H magnetic resonance spectra. Neurochem Res 2014; 39 (01) 1-36
• 92 Schür RR, Draisma LWR, Wijnen JP. , et al. Brain GABA levels across psychiatric disorders: A systematic literature review and meta-analysis of (1) H-MRS studies. Hum Brain Mapp 2016; 37 (09) 3337-3352
• 93 Aoki Y, Kasai K, Yamasue H. Age-related change in brain metabolite abnormalities in autism: a meta-analysis of proton magnetic resonance spectroscopy studies. Transl Psychiatry 2012; 2: e69
• 94 Lam KS, Aman MG, Arnold LE. Neurochemical correlates of autistic disorder: a review of the literature. Res Dev Disabil 2006; 27 (03) 254-289
• 95 Vasconcelos MM, Brito AR, Domingues RC. , et al. Proton magnetic resonance spectroscopy in school-aged autistic children. J Neuroimaging 2008; 18 (03) 288-295