Restricted accessResearch articleFirst published online 2020-02-18
Reduced Hippocampal Glutamate and Posterior Cingulate N-Acetyl Aspartate in Mild Cognitive Impairment and Alzheimer’s Disease Is Associated with Episodic Memory Performance and White Matter Integrity in the Cingulum: A Pilot Study
Identification of biological changes underlying the early symptoms of Alzheimer’s disease (AD) will help to identify and stage individuals prior to symptom onset. The limbic system, which supports episodic memory and is impaired early in AD, is a primary target. In this study, brain metabolism and microstructure evaluated by high field (7 Tesla) proton magnetic resonance spectroscopy (1H-MRS) and diffusion tensor imaging (DTI) were evaluated in the limbic system of eight individuals with mild cognitive impairment (MCI), nine with AD, and sixteen normal elderly controls (NEC). Left hippocampal glutamate and posterior cingulate N-acetyl aspartate concentrations were reduced in MCI and AD compared to NEC. Differences in DTI metrics indicated volume and white matter loss along the cingulum in AD compared to NEC. Metabolic and microstructural changes were associated with episodic memory performance assessed using Craft Story 21 Recall and Benson Complex Figure Copy. The current study suggests that metabolite concentrations measured using 1H-MRS may provide insight into the underlying metabolic and microstructural processes of episodic memory impairment.
ScheltensP, BlennowK, BretelerMMB, de StrooperB, FrisoniGB, SallowayS, Van der FlierWM (2016) Alzheimer’s disease. Lancet388, 505–517.
2.
QuerfurthHW, LaFerlaFM (2010) Alzheimer’s disease. N Engl J Med362, 329–344.
3.
AlbertMS, DeKoskyST, DicksonD, DuboisB, FeldmanHH, FoxNC, GamstA, HoltzmanDM, JagustWJ, PetersenRC, SnyderPJ, CarrilloMC, ThiesB, PhelpsCH (2011) The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement7, 270–279.
4.
McKhannGM, KnopmanDS, ChertkowH, HymanBT, JackCR, KawasCH, KlunkWE, KoroshetzWJ, ManlyJJ, MayeuxR, MohsRC, MorrisJC, RossorMN, ScheltensP, CarrilloMC, ThiesB, WeintraubS, PhelpsCH (2011) The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement7, 263–269.
5.
JackCR, LoweVJ, SenjemML, WeigandSD, KempBJ, ShiungMM, KnopmanDS, BoeveBF, KlunkWE, MathisCA, PetersenRC (2008) 11C PiB and structural MRI provide complementary information in imaging of Alzheimer’s disease and amnestic mild cognitive impairment. Brain131, 665–680.
6.
KantarciK, MurrayME, SchwarzCG, ReidRI, PrzybelskiSA, LesnickT, ZukSM, RamanMR, SenjemML, GunterJL, BoeveBF, KnopmanDS, ParisiJE, PetersenRC, JackCR, DicksonDW (2017) White-matter integrity on DTI and the pathologic staging of Alzheimer’s disease. Neurobiol Aging56, 172–179.
7.
SperlingR (2011) The potential of functional MRI as a biomarker in early Alzheimer’s disease. Neurobiol Aging32, S37–S43.
8.
MosconiL, BertiV, GlodzikL, PupiA, De SantiS, De LeonMJ (2010) Pre-clinical detection of Alzheimer’s disease using FDG-PET, with or without amyloid imaging. J Alzheimers Dis20, 843–854.
SolomonPR, MurphyCA (2008) Early diagnosis and treatment of Alzheimer’s disease. Expert Rev Neurother8, 769–780.
11.
WangH, TanL, WangHF, LiuY, YinRH, WangWY, ChangXL, JiangT, YuJT (2015) Magnetic resonance spectroscopy in Alzheimer’s disease: Systematic review and meta-analysis. J Alzheimers Dis46, 1049–1070.
12.
BubbEJ, Metzler-BaddeleyC, AggletonJP (2018) The cingulum bundle: Anatomy, function, and dysfunction. Neurosci Biobehav Rev92, 104–127.
13.
GranzieraC, HadjikhaniN, ArzyS, SeeckM, MeuliR, KruegerG (2011) In-vivo magnetic resonance imaging of the structural core of the Papez circuit in humans. Neuroreport22, 227–231.
MoriS, AggarwalM (2014) In vivo magnetic resonance imaging of the human limbic white matter. Front Aging Neurosci6, 321.
16.
ShahA, JhawarSS, GoelA (2012) Analysis of the anatomy of the Papez circuit and adjoining limbic system by fiber dissection techniques. J Clin Neurosci19, 289–298.
17.
HornbergerM, WongS, TanR, IrishM, PiguetO, KrilJ, HodgesJR, HallidayG (2012) In vivo and post-mortem memory circuit integrity in frontotemporal dementia and Alzheimer’s disease. Brain135, 3015–3025.
18.
LockhartSN, MaydaAB, RoachAE, FletcherE, CarmichaelO, MaillardP, SchwarzCG, YonelinasAP, RanganathC, DeCarliC (2012) Episodic memory function is associated with multiple measures of white matter integrity in cognitive aging. Front Hum Neurosci6, 56.
19.
TanRH, WongS, KrilJJ, PiguetO, HornbergerM, HodgesJR, HallidayGM (2014) Beyond the temporal pole: Limbic memory circuit in the semantic variant of primary progressive aphasia. Brain137, 2065–2076.
20.
BäckmanL, JonesS, BergerA-K, LaukkaEJ, SmallBJ (2005) Cognitive impairment in preclinical Alzheimer’s disease: A meta-analysis. Neuropsychology19, 520–531.
21.
GoldCA, BudsonAE (2008) Memory loss in Alzheimer’s disease: Implications for development of therapeutics. Expert Rev Neurother8, 1879–1891.
22.
ChooIH, LeeDYS, OhJS, LeeJS, LeeDYS, SongIC, YounJC, KimSG, KimKW, JhooJH, WooJI (2010) Posterior cingulate cortex atrophy and regional cingulum disruption in mild cognitive impairment and Alzheimer’s disease. Neurobiol Aging31, 772–779.
23.
MorraJH, TuZ, ApostolovaLG, GreenAE, AvedissianC, MadsenSK, ParikshakN, TogaAW, JackCR, SchuffN, WeinerMW, ThompsonPM (2009) Automated mapping of hippocampal atrophy in 1-year repeat MRI data from 490 subjects with Alzheimer’s disease, mild cognitive impairment, and elderly controls. Neuroimage45, S3–S15.
24.
MutluJ, LandeauB, TomadessoC, de FloresR, MézengeF, de La SayetteV, EustacheF, ChételatG (2016) Connectivity disruption, atrophy, and hypometabolism within posterior cingulate networks in Alzheimer’s disease. Front Neurosci10, 582.
25.
SchuffN, WoernerN, BoretaL, KornfieldT, ShawLM, TrojanowskiJQ, ThompsonPM, JackCR, WeinerMW (2009) MRI of hippocampal volume loss in early Alzheimers disease in relation to ApoE genotype and biomarkers. Brain132, 1067–1077.
YuJ, LamCLM, LeeTMC (2017) White matter microstructural abnormalities in amnestic mild cognitive impairment: A meta-analysis of whole-brain and ROI-based studies. Neurosci Biobehav Rev83, 405–416.
30.
ZhangY, SchuffN, JahngGH-H, BayneW, MoriS, SchadL, MuellerS, DuA-TT, KramerJH, YaffeK, ChuiH, JagustWJ, MillerBL, WeinerMW (2007) Diffusion tensor imaging of cingulum fibers in mild cognitive impairment and Alzheimer disease. Neurology68, 13–19.
31.
De SantiS, De LeonMJ, RusinekH, ConvitA, TarshishCY, RocheA, TsuiWH, KandilE, BoppanaM, DaisleyK, WangGJ, SchlyerD, FowlerJ (2001) Hippocampal formation glucose metabolism and volume losses in MCI and AD. Neurobiol Aging22, 529–539.
32.
JackCR, KnopmanDS, JagustWJ, ShawLM, AisenPS, WeinerMW, PetersenRC, TrojanowskiJQ (2010) Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol9, 119–128.
33.
ReimanEM, UeckerA, CaselliRJ, LewisS, BandyD, De LeonMJ, De SantiS, ConvitA, OsborneD, WeaverA, ThibodeauSN (1998) Hippocampal volumes in cognitively normal persons at genetic risk for Alzheimer’s disease. Ann Neurol44, 288–291.
DixonRMR, BradleyKKM, BudgeMMM, StylesP, SmithAD (2002) Longitudinal quantitative proton magnetic resonance spectroscopy of the hippocampus in Alzheimer’s disease. Brain125, 2332–2341.
KantarciK, SmithGE, IvnikRJ, PetersenRC, BoeveBF, KnopmanDS, TangalosEG, JackCR (2002) 1H magnetic resonance spectroscopy, cognitive function, and apolipoprotein E genotype in normal aging, mild cognitive impairment and Alzheimer’s disease. J Int Neuropsychol Soc8, 934–942.
FoyCML, DalyEM, GloverA, O’GormanR, SimmonsA, MurphyDGM, LovestoneS (2011) Hippocampal proton MR spectroscopy in early Alzheimer’s disease and mild cognitive impairment. Brain Topogr24, 316–322.
41.
WatanabeT, ShiinoA, AkiguchiI (2012) Hippocampal metabolites and memory performances in patients with amnestic mild cognitive impairment and Alzheimer’s disease. Neurobiol Learn Mem97, 289–293.
42.
WatanabeT, ShiinoA, AkiguchiI (2010) Absolute quantification in proton magnetic resonance spectroscopy is useful to differentiate amnesic mild cognitive impairment from Alzheimer’s disease and healthy aging. Dement Geriatr Cogn Disord30, 71–77.
43.
FayedN, ModregoPJ, Rojas-SalinasG, AguilarK (2011) Brain glutamate levels are decreased in Alzheimer’s disease. Am J Alzheimers Dis Other Demen26, 450–456.
44.
PetersenRC (2004) Mild cognitive impairment as a diagnostic entity. J Intern Med256, 183–194.
WinbladB, PalmerK, KivipeltoM, JelicV, FratiglioniL, WahlundLO, NordbergA, BäckmanL, AlbertM, AlmkvistO, AraiH, BasunH, BlennowK, De LeonM, DecarliC, ErkinjunttiT, GiacobiniE, GraffC, HardyJ, JackC, JormA, RitchieK, Van DuijnC, VisserP, PetersenRC (2004) Mild cognitive impairment - Beyond controversies, towards a consensus: Report of the International Working Group on Mild Cognitive Impairment. J Intern Med256, 240–246.
47.
McKhannG, DrachmanD, FolsteinM, KatzmanR, PriceD, StadlanEM (1984) Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology34, 939–939.
48.
WeinerMW, VeitchDP, AisenPS, BeckettLA, CairnsNJ, GreenRC, HarveyD, JackCR, JagustW, LiuE, MorrisJC, PetersenRC, SaykinAJ, SchmidtME, ShawL, ShenL, SiuciakJA, SoaresH, TogaAW, TrojanowskiJQ (2013) The Alzheimer’s Disease Neuroimaging Initiative: A review of papers published since its inception. Alzheimers Dement9, e111–e194.
49.
GilbertKM, GatiJS, KhoE, Martyn KlassenL, ZemanP, MenonR (2015) An parallel-transmit, parallel-receive coil for routine scanning on a 7T head-only scanner. In Proceedings of the 23rd Annual Meeting of ISMRM, Toronto, pp. 0623.
50.
MarquesJP, KoberT, KruegerG, van der ZwaagW, Van de MoorteleP-F, GruetterR (2010) MP2RAGE, a self bias-field corrected sequence for improved segmentation and T1-mapping at high field. Neuroimage49, 1271–1281.
51.
GarwoodM, DelaBarreL (2001) The return of the frequency sweep: Designing adiabatic pulses for contemporary NMR. J Magn Reson153, 155–177.
52.
OzG, TkáčI (2011) Short-echo, single-shot, full-intensity proton magnetic resonance spectroscopy for neurochemical profiling at 4 T: Validation in the cerebellum and brainstem. Magn Reson Med65, 901–910.
53.
WongD, SchranzAL, BarthaR (2018) Optimized in vivo brain glutamate measurement using long-echo-time semi-LASER at 7 T. NMR Biomed31, e4002.
JenkinsonM, BannisterP, BradyM, SmithS (2002) Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage17, 825–841.
59.
JenkinsonM, SmithS (2001) A global optimisation method for robust affine registration of brain images. Med Image Anal5, 143–156.
SmithSM, JenkinsonM, WoolrichMW, BeckmannCF, BehrensTEJ, Johansen-BergH, BannisterPR, De LucaM, DrobnjakI, FlitneyDE, NiazyRK, SaundersJ, VickersJ, ZhangY, De StefanoN, BradyJM, MatthewsPM (2004) Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage23, S208–S219.
62.
WoolrichMW, JbabdiS, PatenaudeB, ChappellM, MakniS, BehrensT, BeckmannC, JenkinsonM, SmithSM (2009) Bayesian analysis of neuroimaging data in FSL. Neuroimage45, S173–S186.
63.
AnderssonJLR, SkareS, AshburnerJ (2003) How to correct susceptibility distortions in spin-echo echo-planar images: Application to diffusion tensor imaging. Neuroimage20, 870–888.
64.
AnderssonJLR, SotiropoulosSN (2016) An integrated approach to correction for off-resonance effects and subject movement in diffusion MR imaging. Neuroimage125, 1063–1078.
65.
BarthaR, DrostDJ, MenonRS, WilliamsonPC (2000) Spectroscopic lineshape correction by QUECC: Combined QUALITY deconvolution and eddy current correction. Magn Reson Med44, 641–645.
66.
De GraafAA, Van DijkJE, BoéEWMMJ (1990) QUALITY: Quantification improvement by converting lineshapes to the lorentzian type. Magn Reson Med13, 343–357.
67.
BarthaR, DrostDJ, WilliamsonPC (1999) Factors affecting the quantification of short echo in-vivo 1H MR spectra: Prior knowledge, peak elimination, and filtering. NMR Biomed12, 205–216.
68.
MarquardtDW (1963) An algorithm for least-squares estimation of nonlinear parameters. J Soc Ind Appl Math11, 431–441.
69.
MarjańskaM, AuerbachEJ, ValabrègueR, Van de MoorteleP-F, AdrianyG, GarwoodM (2012) Localized 1H NMR spectroscopy in different regions of human brain in vivo at 7 T: T2 relaxation times and concentrations of cerebral metabolites. NMR Biomed25, 332–339.
70.
GasparovicC, SongT, DevierD, BockholtHJ, CaprihanA, MullinsPG, PosseS, JungRE, MorrisonLA (2006) Use of tissue water as a concentration reference for proton spectroscopic imaging. Magn Reson Med55, 1219–1226.
71.
ZhangY, BradyM, SmithS (2001) Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. IEEE Trans Med Imaging20, 45–57.
72.
RooneyWD, JohnsonG, LiX, CohenER, KimSG, UgurbilK, SpringerCS (2007) Magnetic field and tissue dependencies of human brain longitudinal 1H2O relaxation in vivo. Magn Reson Med57, 308–318.
73.
de GraafRA (2007) In Vivo NMR Spectroscopy, John Wiley & Sons, Ltd, Chichester, UK.
74.
RyanK, WawrzynK, GatiJS, ChronikBA, WongD, DuggalN, BarthaR (2018) 1H MR spectroscopy of the motor cortex immediately following transcranial direct current stimulation at 7 Tesla. PLoS One13, e0198053.
75.
WakanaS, CaprihanA, PanzenboeckMM, FallonJH, PerryM, GollubRL, HuaK, ZhangJ, JiangH, DubeyP, BlitzA, van ZijlP, MoriS (2007) Reproducibility of quantitative tractography methods applied to cerebral white matter. Neuroimage36, 630–644.
76.
FrimanO, FarnebackG, WestinC-F (2006) A Bayesian approach for stochastic white matter tractography. IEEE Trans Med Imaging25, 965–978.
77.
HuaK, ZhangJ, WakanaS, JiangH, LiX, ReichDS, CalabresiPA, PekarJJ, van ZijlPCM, MoriS (2008) Tract probability maps in stereotaxic spaces: Analyses of white matter anatomy and tract-specific quantification. Neuroimage39, 336–347.
78.
MoriS, CrainBJ (2005), MRI atlas of human white matter, Elsevier.
79.
FowlkesC, BelongieS, ChungF, MalikJ (2004) Spectral grouping using the Nyström method. IEEE Trans Pattern Anal Mach Intell26, 214–225.
80.
Von LuxburgU (2007) A tutorial on spectral clustering. Stat Comput17, 395–416.
GrubbsFE (1969) Procedures for detecting outlying observations in samples. Technometrics11, 1–21.
83.
HowellDC (2013), Fundamental Statistics for the Behavioral Sciences.
84.
R Development Core Team (2008) R: A Language and Environment for Statistical Computing.
85.
AriyannurPS, MoffettJR, ManickamP, PattabiramanN, ArunP, NittaA, NabeshimaT, MadhavaraoCN, NamboodiriAMA (2010) Methamphetamine-induced neuronal protein NAT8L is the NAA biosynthetic enzyme: Implications for specialized acetyl coenzyme A metabolism in the CNS. Brain Res1335, 1–13.
86.
Del SoleA, ClericiF, ChitiA, LecchiM, MarianiC, MaggioreL, MosconiL, LucignaniG (2008) Individual cerebral metabolic deficits in Alzheimer’s disease and amnestic mild cognitive impairment: An FDG PET study. Eur J Nucl Med Mol Imaging35, 1357–1366.
87.
MinoshimaS, FosterNL, SimaAAF, FreyKA, AlbinRL, KuhlDE (2001) Alzheimer’s disease versus dementia with Lewy bodies: Cerebral metabolic distinction with autopsy confirmation. Ann Neurol50, 358–365.
88.
MosconiL, TsuiWH, HerholzK, PupiA, DrzezgaA, LucignaniG, ReimanEM, HolthoffV, KalbeE, SorbiS, Diehl-SchmidJ, PerneczkyR, ClericiF, CaselliR, Beuthien-BaumannB, KurzA, MinoshimaS, de LeonMJ (2008) Multicenter standardized 18F-FDG PET diagnosis of mild cognitive impairment, Alzheimer’s disease, and other dementias. J Nucl Med49, 390–398.
89.
OssenkoppeleR, TolboomN, Foster-DingleyJC, AdriaanseSF, BoellaardR, YaqubM, WindhorstAD, BarkhofF, LammertsmaAA, ScheltensP, Van Der FlierWM, Van BerckelBNM (2012) Longitudinal imaging of Alzheimer pathology using [11C]PIB, [18F]FDDNP and [18F]FDG PET. Eur J Nucl Med Mol Imaging39, 990–1000.
90.
BaslowMH, SuckowRF, SapirsteinV, HungundBL (1999) Expression of aspartoacylase activity in cultured rat macroglial cells is limited to oligodendrocytes. J Mol Neurosci13, 47–53.
91.
MadhavaraoCN, MoffettJR, MooreRA, ViolaRE, NamboodiriMA, JacobowitzDM (2004) Immunohistochemical localization of aspartoacylase in the rat central nervous system. J Comp Neurol472, 318–329.
92.
MoffettJR, ArunP, AriyannurPS, GarbernJY, JacobowitzDM, NamboodiriAMA (2011) Extensive aspartoacylase expression in the rat central nervous system. Glia59, 1414–1434.
93.
MoffettJR, RossB, ArunP, MadhavaraoCN, NamboodiriMAA (2007) N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology. Prog Neurobiol81, 89–131.
94.
FeldmanHM, YeatmanJD, LeeES, BardeLHF, Gaman-BeanS (2010) Diffusion tensor imaging: A review for pediatric researchers and clinicians. J Dev Behav Pediatr31, 346–356.
95.
ThompsonPM, HayashiKM, De ZubicarayGI, JankeAL, RoseSE, SempleJ, HongMS, HermanDH, GravanoD, DoddrellDM, TogaAW (2004) Mapping hippocampal and ventricular change in Alzheimer disease. Neuroimage22, 1754–1766.
96.
AlexanderAL, LeeJE, LazarM, FieldAS (2007) Diffusion tensor imaging of the brain. Neurotherapeutics4, 316–329.
97.
BarcoA, BaileyCH, KandelER (2006) Common molecular mechanisms in explicit and implicit memory. J Neurochem97, 1520–1533.
98.
TammingaCA, SouthcottS, SaccoC, WagnerAD, GhoseS (2012) Glutamate dysfunction in hippocampus: Relevance of dentate gyrus and CA3 signaling. Schizophr Bull38, 927–935.
99.
NestorPJ, FryerTD, SmielewskiP, HodgesJR (2003) Limbic hypometabolism in Alzheimer’s disease and mild cognitive impairment. Ann Neurol54, 343–351.
100.
YudkoffM, NelsonD, DaikhinY, ErecińskaM (1994) Tricarboxylic acid cycle in rat brain synaptosomes. Fluxes and interactions with aspartate aminotransferase and malate/aspartate shuttle. J Biol Chem269, 27414–27420.
101.
HarrisK, LinA, BhattacharyaP, TranT, WongW, RossB (2006) Regulation of NAA-synthesis in the human brain in vivo: Canavan’s disease, Alzheimer’s disease and schizophrenia. Adv Exp Med Biol576, 263–273; discussion 361-363.
102.
LakensD (2013) Calculating and reporting effect sizes to facilitate cumulative science: A practical primer for t-tests and ANOVAs. Front Psychol4, 863.
103.
OlejnikS, AlginaJ (2003) Generalized eta and omega squared statistics: Measures of effect size for some common research designs. Psychol Methods8, 434–447.
104.
SuL, BlamireAM, WatsonR, HeJ, HayesL, O’BrienJT (2016) Whole-brain patterns of 1H-magnetic resonance spectroscopy imaging in Alzheimer’s disease and dementia with Lewy bodies. Transl Psychiatry6, e877.
105.
SchottJM, FrostC, MacManusDG, IbrahimF, WaldmanAD, FoxNC (2010) Short echo time proton magnetic resonance spectroscopy in Alzheimer’s disease: A longitudinal multiple time point study. Brain133, 3315–3322.
106.
SextonCE, KaluUG, FilippiniN, MackayCE, EbmeierKP (2011) A meta-analysis of diffusion tensor imaging in mild cognitive impairment and Alzheimer’s disease. Neurobiol Aging32, 2322.e5–2322.e18.
107.
CathelineG, PeriotO, AmiraultM, BraunM, DartiguesJF, AuriacombeS, AllardM (2010) Distinctive alterations of the cingulum bundle during aging and Alzheimer’s disease. Neurobiol Aging31, 1582–1592.
108.
ErdfelderE, FAulF, BuchnerA, LangAG (2009) Statistical power analyses using G*Power 3.1: Tests for correlation and regression analyses. Behav Res Methods41, 1149–1160.
109.
TschanzJT, CorcoranCD, SchwartzS, TreiberK, GreenRC, NortonMC, MielkeMM, PiercyK, SteinbergM, RabinsPV, LeoutsakosJM, Welsh-BohmerKA, BreitnerJCS, LyketsosCG (2011) Progression of cognitive, functional, and neuropsychiatric symptom domains in a population cohort with Alzheimer dementia: The cache county dementia progression study. Am J Geriatr Psychiatry19, 532–542.
BaiX, EddenRAE, GaoF, WangG, WuL, ZhaoB, WangM, ChanQ, ChenW, BarkerPB (2015) Decreased γ-aminobutyric acid levels in the parietal region of patients with Alzheimer’s disease. J Magn Reson Imaging41, 1326–1331.
114.
ZhangY, ZhangJ, OishiK, FariaAV, JiangH, LiX, AkhterK, Rosa-NetoP, PikeGB, EvansA, TogaAW, WoodsR, MazziottaJC, MillerMI, van ZijlPC, MoriS (2010) Atlas-guided tract reconstruction for automated and comprehensive examination of the white matter anatomy. Neuroimage52, 1289–1301.
115.
ZhangW, OliviA, HertigSJ, van ZijlP, MoriS (2008) Automated fiber tracking of human brain white matter using diffusion tensor imaging. Neuroimage42, 771–777.
116.
XinL, SchallerB, MlynarikV, LuH, GruetterR (2013) Proton T1 relaxation times of metabolites in human occipital white and gray matter at 7 T. Magn Reson Med69, 931–936.
117.
AndreychenkoA, KlompDWJ, De GraafRA, LuijtenPR, BoerVO (2013) In vivo GABA T2 determination with J-refocused echo time extension at 7 T. NMR Biomed26, 1596–1601.
118.
KreisR, SlotboomJ, HofmannL, BoeschC (2005) Integrated data acquisition and processing to determine metabolite contents, relaxation times, and macromolecule baseline in single examinations of individual subjects. Magn Reson Med54, 761–768.
