Magnetická rezonancia Pohľad do mozgu

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1 VEDECKÁ KAVIAREŇ Centrum pre vedecko-technicke informacie 24. marec 2011 Magnetická rezonancia Pohľad do mozgu Ivan Tkáč Center for Magnetic Resonance Research UNIVERSITY OF MINNESOTA

2 Obsah prednášky história magnetickej rezonancie funkčná magnetická rezonancia difúzia a MR zobrazovanie MR spektroskopia

3 Medzníky v histórii rozvoja magnetickej rezonancie spin Wolfgang Pauli (1927) relativistická kvantová mechanika Paul Dirac (1928) prvé experimentálne dôkazy nukleárej magnetickej rezonancie (NMR) Isidor Rabi (1938, Nobelová cena 1944) NMR v kvapalinách a tuhej faze Felix Bloch a Edward Purcell (1945, Nobelová cena 1952) FT NMR Richard Ernst (Nobelová cena 1991) štrukturálna analýza bio-makromolekul v roztokoch s použitím NMR Kurt Wüthrich (Nobelová cena 1992)

4 Medzníky v histórii rozvoja MR zobrazovania prvé zobrazenie na princípe MR (1973) prvý obrázok ľudského tela (1977) Nobelová cena za MR zobrazovanie: Paul Lauterbour a Peter Mansfield (2003) prvé dva MR tomografy na Slovensku Bratislava, Dérerova nemocnica na Kramároch (1992)

5 Magnetic Resonance Imaging (MRI)

6 Funkčná magnetická rezonancia základné princípy funkčného zobrazovania príklady

7 Functional Magnetic Resonance Imaging (fmri) Základný princíp fmri: hemodynamická odozva (zmena prietoku krvi) v dôsledku aktivity nervových buniek mozgu Vizuálna stimulácia zmena prietoku krvi v oblasti occipitálneho laloku

8 Základný princíp fmri základný stav aktivovaný stav neuróny cievna kapilára O 2 O 2 O 2 O 2 zmena pomeru oxyhemoglobin/deoxyhemoglobin

9 BOLD fmri Activation Map / MR Signal over Time 2cm MRI signals from Visual Cortex modulate due to the presentation of a visual stimulus to the subject inside the magnet. Essa Yacoub, CMRR

10 Resting State fmri Different regions in the brain are functionally connected at rest, as depicted by resting state BOLD signal fluctuations which oscillate in synchrony. Essa Yacoub, CMRR

11 MR zobrazovanie s difúznym vážením základné princípy difuzneho váženia anizotropia difuzie MR traktografia

12 Importance of Diffusion MRI White matter: Axonal nerve fibers connecting functional gray matter areas Affected by wide range of diseases: stroke, MS, tumor, Alzheimer s and Parkinson s...etc Diffusion MRI: new landscapes of discoveries for neuroscience & medicine Christophe Lenglet, CMRR

13 Základný princíp difúzneho váženia v MR zobrazovaní izotropná difúzia difúzny tenzor anizotropná difúzia nervové vlákno (axon)

14 Princíp difúzneho váženia 90 o ACQ RF G dif čas

15 Princíp difúzneho váženia 90 o ACQ RF difúzia G dif čas

16 Diffusion Tensor Imaging (DTI) ADC LA FA PA V1 SA

17 High Order Diffusion Models: Q-Ball Imaging Christophe Lenglet, CMRR

18

19 Tractography using Higher Order Models Christophe Lenglet, CMRR

20 Fetal Alcoholism Spectrum Disorder Ryan L. Muetzel, Jeffrey R. Wozniak, CMRR

21 Diffusion Weighted Imaging/Tractography MRI method for the reconstruction of white matter microstructures Human, 7T, 1.5 x 1.5 x 1.5 mm 3 Tractography Noam Harel, CMRR

22 Combination of fmri and DTI to study the resting state brain activity Ryan L. Muetzel, Jeffrey R. Wozniak, CMRR

23 In vivo NMR spektroskopia Magnetic Resonance Spectroscopy (MRS) základné princípy MRS vizuálna stimulácia

24 1 H MR spectrum of glutamate at 7T H 2 N 5 C O 4 H H H 3 2 C C C COOH H H NH ,4 3,3 in vivo linewidth at 7T ppm TKAC, University of Minnesota

25 High-resolution and in vivo 1 H NMR spectroscopy myo-inositol 1 H NMR spectrum OH 5 H H OH H 4 6 OH 1 H OH 3 OH H 2 2 4,6 1,3 5 OH H MRI mouse brain in vivo 1 H NMR spectrum TKAC, University of Minnesota

26 Increased sensitivity at high magnetic fields N β N β /N α = exp(-δe/kt) ΔE = γhb ΔE 0 = /2π γhb 0 /2π N β N α M z ~ N α - N β N α low magnetic field B 0 high magnetic field B 0 TKAC, University of Minnesota

27 Increased spectral resolution at high B 0 myo-inositol OH 5 H H OH H 4 6 OH OH 1 H OH H 3 OH H 2 4,6 1,3 B 0 = 1.5 T B 0 = 9.4 T ppm TKAC, University of Minnesota

28 Effect of increased field strength on separation of glutamine from glutamate [Glu]/[Gln] = 3 1.5T Glu Gln 3T T ppm ppm TKAC, University of Minnesota

29 Simulated high-resolution 1 H NMR spectrum of the human brain at 7T line width typical for in vivo FWHM = 9 Hz NAA PCr PE myo-ins Lac Cr Asc Gln scyllo-ins Glu PC GSH GPC myo-ins Tau Cr PCr GABA GSH Asp Gln NAA GABA Glu NAAG Gln Glu GABA NAAG macromolecules Ala Lac TKAC, University of Minnesota

30 Comparison of simulated and experimental data experimental simulated spectrum human brain 7T ppm TKAC, University of Minnesota

31 Requirements on 1 H MR spectrum quality for reliable metabolite quantification PCr Cr shimming spectral resolution Asc GSH Gln Glu myo-ins myo-ins GPC PC myo-ins scyllo-ins Tau human brain at 7T STEAM TE = 6 ms flat baseline efficient water suppression localization performance (no lipid contamination) SNR ppm TKAC, University of Minnesota

32 Brain metabolites detectable by 1 H MRS at 7T Ascorbate quantification NAA Ins Cr PCr Asc Gln Glu GSH Ins Tau Cr PCr Asp Glu Gln NAA in vivo spectrum Glu MM Gln Asc GSH myo-ins scyllo-ins ppm TKAC, University of Minnesota

33 Brain metabolites detectable by 1 H MRS at 7T NAA Ins Cr PCr Asc Gln Glu GSH Ins Tau Cr PCr Asp Glu Glu NAA in vivo spectrum PCr Cr GABA GPC PC Asp ppm TKAC, University of Minnesota

34 Brain metabolites detectable by 1 H MRS at 7T NAA Ins Cr PCr Asc Gln Glu GSH Ins Tau Cr PCr Asp Glu Glu NAA in vivo spectrum Tau Gly PE NAA NAAG Lac ppm TKAC, University of Minnesota

35 Single scan in vivo 1 H MR spectrum of the human brain at 7 T FASTMAP shimming STEAM TE = 6 ms TR = 5 s VOI = 8 ml VAPOR water suppression NT = ppm Tkac, Appl Magn Reson 2005 TKAC, University of Minnesota

36 Comparison of 1 H MR spectroscopy at 4T and 7T B 0 = 4T B 0 = 7T SNR 7T / SNR 4T ~ ppm ppm TKAC, University of Minnesota

37 Asc Asp Cr PCr GABA Gln Glu GSH myo-ins scyllo-ins Lac NAA NAAG PE PC GPC Tau NAA+NAAG GPC+PC Cr+PCr concentration (µmol/g) Comparison of metabolite quantification at 4T and 7T gray-matter-rich occipital cortex, 10 subjects T 7T Tkac, Magn Reson Med 2009 TKAC, University of Minnesota

38 In vivo 1 H NMR spectrum from the visual cortex ON ON OFF OFF OFF min NAA NT = 32 time resolution = 2.7 min SNR ~ 180 residual water Ins Cr PCr scyllo-ins Gln Glu Tau Ins Cho Cr PCr Asp Glu Gln NAA Lac ppm Mangia et al, J Cereb Blood Flow Metab 2007 TKAC, University of Minnesota

39 variation in signal height of Cr (%) Lac concentration (µmol/g) group average Concentration changes of Lac during stimulation subject # 1 ON ON OFF OFF OFF # 2 time resolution = 20 s # min time lactate resolution trajectory = 2.7 min BOLD effect on metabolites Mangia et al, J Cereb Blood Flow Metab 2007 TKAC, University of Minnesota

40 Concentration changes of brain metabolites ON ON OFF OFF OFF moving average time resolution = 40 s min (mean ± SEM) Mangia et al, J Cereb Blood Flow Metab 2007 TKAC, University of Minnesota

41 Summed spectra from all subjects and both stimulation paradigms difference x 20 visual stimulation resting period NT = 1536 FT, no weighting ppm TKAC, University of Minnesota

42 LCModel analysis of the difference spectrum residual Asp Glc Glu Lac LCModel fit difference (x 30) difference FWHM = 9.5 Hz FWHM = 10.0 Hz FWHM µmol/g µmol/g µmol/g µmol/g difference lb = 0.4 Hz Hz difference ppm TKAC, University of Minnesota

43 Proposed scheme of cerebral metabolism Glc plasma BBB Mitochondrion Glc cytosol CMR Glc NAD + NADH Gjedde and Marrett 2001 Dienel and Cruz 2003 Pyruvate Lac efflux Lac BBB TCA cycle CMR O2 Lac plasma TKAC, University of Minnesota

44 Proposed scheme of cerebral metabolism Glc plasma BBB Mitochondrion Glc cytosol malate malate H + NAD + CMR Glc NAD + 2-OG Glu Glu 2-OG NADH NADH OAA Asp Asp OAA pyruvate Lac efflux Lac BBB TCA cycle CMR O2 Lac plasma Mangia et al, J Cereb Blood Flow Metab 2007 TKAC, University of Minnesota

45 Nové progresívne metódy magnetickej rezonancie neinvazivný charakter MR metód fmri mapovanie funkčných vlastností DTI/HARDI mikroštruktúra mozgu MRS neurochémia Potenciál nových metód MR Skvalitnenie medecinskej diagnostiky a terapie

46 NMR spektroskopia na Slovensku V ramci štátneho programu budovania infraštruktúry výrazná investícia do modernizácie NMR pristrojovej techniky Národné centrum NMR spektroskopie Slovenská Technická Univerzita Univerzita Komenského Univerzita Pavla Jozefa Šafárika Technická Univerzita Košice Chemický Ústav SAV Ústav Merania SAV Univerzitná Nemocnica Ladislava Dérera

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