title: An MRspec database query and visualization engine with applications as a clinical diagnostic and research tool.
abstract: Proton magnetic resonance spectroscopy (MRspec), one of the very few techniques for in vivo assessment of neuro-metabolic profiles, is often complicated by lack of standard population norms and paucity of computational tools.
  
  
  
  7035 scans and clinical information from 4430 pediatric patients were collected from 2008 to 2014. Scans were conducted using a 1.5T (n=3664) or 3T scanner (n=3371), and with either a long (144ms, n=5559) or short echo time (35ms, n=1476). 3055 of these scans were localized in the basal ganglia (BG), 1211 in parieto-occipital white matter (WM). 34 metabolites were quantified using LCModel. A web application using MySQL, Python and Flask was developed to facilitate the exploration of the data set.
  
  
  
  Already piloting the application revealed numerous insights. (1), N-acetylaspartate (NAA) increased throughout all ages. During early infancy, total choline was highly varied and myo-inositol demonstrated a downward trend. (2), Total creatine (tCr) and creatine increased throughout childhood and adolescence, though phosphocreatine (PCr) remained constant beyond 200days. (3), tCr was higher in BG than WM. (4), No obvious gender-related differences were observed. (5), Field strength affects quantification using LCModel for some metabolites, most prominently for tCr and total NAA. (6), Outlier analysis identified patients treated with vigabatrin through elevated γ-aminobutyrate, and patients with Klippel-Feil syndrome, Leigh disease and L2-hydroxyglutaric aciduria through low choline in BG.
  
  
  
  We have established the largest MRSpec database and developed a robust and flexible computational tool for facilitating the exploration of vast metabolite datasets that proved its value for discovering neurochemical trends for clinical diagnosis, treatment monitoring, and research. Open access will lead to its widespread use, improving the diagnostic yield and contributing to better understanding of metabolic processes and conditions in the brain.
authors.affiliation: Centre for Computational Medicine, Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, Canada; Department of Computer Science, University of Toronto, Toronto, Canada.
authors.forename: Filip
authors.initials: F
authors.lastname: Miscevic
authors.affiliation: Centre for Computational Medicine, Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Justin
authors.initials: J
authors.lastname: Foong
authors.affiliation: Department of Paediatrics, University of Toronto, Toronto, Canada; Siemens Healthcare, Sydney, Australia; Genetics and Genome Biology, Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Schmitt
authors.affiliation: Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: Blaser
authors.affiliation: Centre for Computational Medicine, Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, Canada; Department of Computer Science, University of Toronto, Toronto, Canada; Genetics and Genome Biology, Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Brudno
authors.affiliation: Department of Paediatrics, University of Toronto, Toronto, Canada; Genetics and Genome Biology, Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, Canada; Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Canada. Electronic address: andreas.schulze@sickkids.ca.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schulze
mesh_terms: D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001479:Basal Ganglia / Q000378:metabolism* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D007294:Inositol / Q000378:metabolism; D007714:Klippel-Feil Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D007888:Leigh Disease / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D066244:Proton Magnetic Resonance Spectroscopy; D066127:White Matter / Q000378:metabolism* / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D001224:Aspartic Acid; D007294:Inositol; D005680:gamma-Aminobutyric Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline
keywords: Clinical dataset; Computational analysis; Inborn errors of metabolism; MRSpec; Magnetic resonance spectroscopy; Neurochemical profiling