title: Comparison of inter subject variability and reproducibility of whole brain proton spectroscopy.
abstract: The aim of these studies was to provide reference data on intersubject variability and reproducibility of metabolite ratios for Choline/Creatine (Cho/Cr), N-acetyl aspartate/Choline (NAA/Cho) and N-acetyl aspartate/Creatine (NAA/Cr), and individual signal-intensity normalised metabolite concentrations of NAA, Cho and Cr. Healthy volunteers underwent imaging on two occasions using the same 3T Siemens Verio magnetic resonance scanner. At each session two identical Metabolic Imaging and Data Acquisition Software (MIDAS) sequences were obtained along with standard structural imaging. Metabolite maps were created and regions of interest applied in normalised space. The baseline data from all 32 volunteers were used to calculate the intersubject variability, while within session and between session reproducibility were calculated from all the available data. The reproducibility of measurements were used to calculate the overall and within session 95% prediction interval for zero change. The within and between session reproducibility data were lower than the values for intersubject variability, and were variable across the different brain regions. The within and between session reproducibility measurements were similar for Cho/Cr, NAA/Choline, Cho and Cr (11.8%, 11.4%, 14.3 and 10.6% vs. 11.9%, 11.4%, 13.5% and 10.5% respectively), but for NAA/Creatine and NAA between session reproducibility was lower (9.3% and 9.1% vs. 10.1% and 9.9%; p <0.05). This study provides additional reference data that can be utilised in interventional studies to quantify change within a single imaging session, or to assess the significance of change in longitudinal studies of brain injury and disease.
authors.affiliation: Department of Critical Care Medicine, University hospitals of Birmingham NHS trust, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom, B15 2TH; Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ.
authors.forename: Tonny V
authors.initials: TV
authors.lastname: Veenith
authors.affiliation: Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom, CB2 0QQ.
authors.forename: Marius
authors.initials: M
authors.lastname: Mada
authors.affiliation: Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Carter
authors.affiliation: Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ.
authors.forename: Julia
authors.initials: J
authors.lastname: Grossac
authors.affiliation: Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ.
authors.forename: Virginia
authors.initials: V
authors.lastname: Newcombe
authors.affiliation: Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ.
authors.forename: Joanne
authors.initials: J
authors.lastname: Outtrim
authors.affiliation: Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom, CB2 0QQ.
authors.forename: Victoria
authors.initials: V
authors.lastname: Lupson
authors.affiliation: Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Nallapareddy
authors.affiliation: Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom, CB2 0QQ.
authors.forename: Guy B
authors.initials: GB
authors.lastname: Williams
authors.affiliation: Department of Radiology, Miller School of Medicine, University of Miami, Miami, Florida, United States of America.
authors.forename: Sulaiman
authors.initials: S
authors.lastname: Sheriff
authors.affiliation: Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ.
authors.forename: David K
authors.initials: DK
authors.lastname: Menon
authors.affiliation: Department of Radiology, Miller School of Medicine, University of Miami, Miami, Florida, United States of America.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Maudsley
authors.affiliation: Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Coles
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping / Q000379:methods*; D002794:Choline / Q000032:analysis*; D003401:Creatine / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D064368:Healthy Volunteers; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging / Q000379:methods; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D012016:Reference Values; D015203:Reproducibility of Results
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline