Magnetická rezonancia
Pohľad do mozgu
Ivan Tkáč
Center for Magnetic Resonance Research
UNIVERSITY OF MINNESOTA
Tkac, University of Minnesota
VEDECKÁ KAVIAREŇCentrum pre vedecko-technicke informacie
24. marec 2011
• história magnetickej rezonancie
Obsah prednášky
• funkčná magnetická rezonancia
• difúzia a MR zobrazovanie
• MR spektroskopia
Tkac, University of Minnesota
• spin – Wolfgang Pauli (1927)
Medzníky v histórii rozvoja magnetickej rezonancie
• 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)
Tkac, University of Minnesota
• prvé zobrazenie na princípe MR – (1973)
Medzníky v histórii rozvoja MR zobrazovania
• prvý obrázok ľudského tela – (1977)
• Nobelová cena za MR zobrazovanie:
Paul Lauterbour a Peter Mansfield – (2003)
Tkac, University of Minnesota
• prvé dva MR tomografy na Slovensku – Bratislava, Dérerova
nemocnica na Kramároch – (1992)
Tkac, University of Minnesota
Funkčná magnetická rezonancia
• základné princípy funkčného zobrazovania
• príklady
Functional Magnetic Resonance Imaging (fMRI)
Tkac, University of Minnesota
Základný princíp fMRI:
hemodynamická odozva (zmena prietoku krvi) v dôsledku aktivity
nervových buniek mozgu
Vizuálna stimulácia
zmena prietoku krvi v oblasti
occipitálneho laloku
Základný princíp fMRI
Tkac, University of Minnesota
O2
O2
O2
O2
cievna kapilára
neuróny
základný stav aktivovaný stav
zmena pomeru
oxyhemoglobin/deoxyhemoglobin
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
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 Tkac, University of Minnesota
Tkac, University of Minnesota
MR zobrazovanie s difúznym vážením
• základné princípy difuzneho váženia
• anizotropia difuzie
• MR traktografia
• 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
Importance of Diffusion MRI
Tkac, University of MinnesotaChristophe Lenglet, CMRR
Základný princíp difúzneho váženia v MR zobrazovaní
Tkac, University of Minnesota
izotropná difúzia
anizotropná difúzia
nervové vlákno (axon)
difúzny tenzor
Fetal Alcoholism Spectrum Disorder
Tkac, University of MinnesotaRyan L. Muetzel, Jeffrey R. Wozniak, CMRR
Diffusion Weighted Imaging/Tractography
MRI method for the
reconstruction of white
matter microstructures
Human, 7T, 1.5 x 1.5 x 1.5 mm3
Tractography
Tkac, University of MinnesotaNoam Harel, CMRR
Combination of fMRI and DTI to study the “resting state” brain activity
Tkac, University of MinnesotaRyan L. Muetzel, Jeffrey R. Wozniak, CMRR
Tkac, University of Minnesota
In vivo NMR spektroskopia
Magnetic Resonance Spectroscopy (MRS)
• základné princípy MRS
• vizuálna stimulácia
C C COOHCH2N
H H NH2
H H H
C
O
4.00 3.75 3.50 3.25 3.00 2.75 2.50 2.25 2.00 ppm
1H MR spectrum of glutamate at 7T
12345
2 3,3’4,4’
TKAC, University of Minnesota
in vivo linewidth at 7T
High-resolution and in vivo 1H NMR spectroscopy
TKAC, University of Minnesota
H
1
2
H
H
H
HH
OH
OHOH
OH
OH
OH
34
5
6
myo-inositol
1,3
4,6
25
1H NMR spectrum
MRI – mouse brain in vivo 1H NMR spectrum
Increased sensitivity at high magnetic fields
Nβ/Nα = exp(-ΔE/kT)
low magnetic field B0 high magnetic field B0
TKAC, University of Minnesota
Nβ
Nα
Nβ
Nα
ΔE = γhB0/2π
Mz ~ Nα - Nβ
ΔE = γhB0/2π
Increased spectral resolution at high B0
myo-inositol
B0 = 1.5 TH
1
2
H
H
H
HH
OH
OHOH
OH
OH
OH
34
5
6
B0 = 9.4 T
1,3
4,6
25
4.2 4.0 3.8 3.6 3.4 3.2 ppm
4.2 3.2
TKAC, University of Minnesota
4.0 3.5 3.0 2.5 2.0 ppm
4 3 2
4.0 3.5 3.0 2.5 2.0 ppm
Effect of increased field strength on separation
of glutamine from glutamate
1.5T
3T
7T
[Glu]/[Gln] = 3
Glu
Gln
TKAC, University of Minnesota
4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5
Lac
NAA
AlaGABA
NAAG
NAAG
Gln
Glu
Gln
NAA
Asp
Cr
PCr
GABA
GSH
PC
GPC
scyllo-Ins
myo-Ins
Tau
Asc
Gln
Glu
GSH
PCr
Cr
myo-Ins
PE
Glu
GABA
Lac
macromolecules
Simulated high-resolution 1H NMR spectrum of
the human brain at 7T
line width typical for in vivo
FWHM = 9 Hz
TKAC, University of Minnesota
5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm
Comparison of simulated and experimental data
experimental spectrumsimulated spectrum
TKAC, University of Minnesota
human brain – 7T
9 ppm8 7 6 5 4 3 2 1 0
flat baseline
efficient
water suppressionSNR
localization performance
(no lipid contamination)
4.2 4.0 3.8 3.6 3.4 3.2
PCr Cr
Asc
GSH
Gln
Glumyo-Ins
Tau
scyllo-Ins
GPC
PC
myo-Ins
myo-Ins
Requirements on 1H MR spectrum quality for
reliable metabolite quantification
shimming
spectral resolution
human brain at 7TSTEAM TE = 6 ms
TKAC, University of Minnesota
in vivo spectrum
MMGlu
Gln
Asc
GSH
myo-Ins
Brain metabolites detectable by 1H MRS at 7TNAA
GluGln
NAA
Asp
Cr
PCr
Ins
Tau
Asc
Gln
Glu
GSH
Ins
Cr
PCr
scyllo-Ins
4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm
TKAC, University of Minnesota
Ascorbate quantification
in vivo spectrum
PCr
Cr
GABA
GPC
PC
Asp
Brain metabolites detectable by 1H MRS at 7T
4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm
NAA
GluGlu
NAA
Asp
Cr
PCr
Ins
Tau
Asc
Gln
Glu
GSH
Ins
Cr
PCr
TKAC, University of Minnesota
in vivo spectrum
Tau
Lac
Brain metabolites detectable by 1H MRS at 7T
4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm
NAA
GluGlu
NAA
Asp
Cr
PCr
Ins
Tau
Asc
Gln
Glu
GSH
Ins
Cr
PCr
Gly
NAAG
NAA
PE
TKAC, University of Minnesota
Single scan in vivo 1H MR spectrum of the human
brain at 7 T
FASTMAP shimming
STEAM
TE = 6 ms TR = 5 s
VOI = 8 ml
NT = 1
Tkac, Appl Magn Reson 2005
6 5 4 3 2 1 ppm0
VAPOR
water suppression
TKAC, University of Minnesota
6 5 4 3 2 1 ppm 6 5 4 3 2 1 ppm
Comparison of 1H MR spectroscopy at 4T and 7T
B0 = 4T B0 = 7T
SNR7T / SNR4T ~ 2
TKAC, University of Minnesota
Comparison of metabolite quantification at 4T and 7T
gray-matter-rich occipital cortex, 10 subjects
0
2
4
6
8
10
12
14
16
A
sc
A
sp
C
r
P
Cr
G
AB
A
G
ln
G
lu
G
SH
my
o-I
ns
sc
yllo
-In
s
L
ac
N
AA
N
AA
G
P
E
P
C
G
PC
T
au
NA
A+
NA
AG
GP
C+
PC
C
r+P
Cr
co
nc
en
tra
tio
n (
µm
ol/g
)
4T 7T
TKAC, University of MinnesotaTkac, Magn Reson Med 2009
6 5 4 3 2 1 ppm
In vivo 1H NMR spectrum from the visual cortex
NT = 32
time resolution = 2.7 min
NAA
NAA
Cr
PCr
Cho
Glu
Ins
Gln
Glu TauGln
Aspresidual
water
scyllo-Ins
Cr
PCr
InsLac
OFF OFF OFF
ON ON
0 4 8 12 16 20 min
SNR ~ 180
Mangia et al, J Cereb Blood Flow Metab 2007 TKAC, University of Minnesota
OFF OFF OFF
ON ON
0 4 8 12 16 20 min
# 1
subject
# 2
#12
Concentration changes of Lac during stimulationg
rou
p a
ve
rag
e
time resolution = 20 s
va
ria
tio
n in
sig
na
l
heig
ht
of
Cr
(%) BOLD effect on metabolites
Lac
co
nce
ntr
ati
on
(µm
ol/
g)
lactate trajectorytime resolution = 2.7 min
•••
Mangia et al, J Cereb Blood Flow Metab 2007 TKAC, University of Minnesota
OFF OFF OFF
ON ON
0 4 8 12 16 20 min
Concentration changes of brain metabolites
moving average
time resolution = 40 s
(mean ± SEM)
Mangia et al, J Cereb Blood Flow Metab 2007 TKAC, University of Minnesota
ppm02345678 1
Summed spectra from all subjects and both
stimulation paradigms
resting period
NT = 1536
FT, no weighting
difference
visual stimulation
x 20
TKAC, University of Minnesota
+0.24 µmol/g
+0.23 µmol/g
-0.13 µmol/g
-0.14 µmol/g
1.01.52.02.53.03.54.0 ppm
residual
Asp
Glc
Glu
Lac
LCModel fit
difference
lb = 0.4 Hz
difference
LCModel analysis of the difference spectrum
-80 -40 0 40 80 Hz
FWHM = 10.0 Hz
FWHM = 9.5 Hz
difference
difference (x 30)
FWHM
TKAC, University of Minnesota
BBB
BBB
Pyruvate Lac
NAD+
NADH
Mitochondrion
Glccytosol
Glcplasma
TCA cycle
Lacplasma
CMRGlc
Proposed scheme of cerebral metabolism
Lac efflux
CMRO2Gjedde and Marrett 2001
Dienel and Cruz 2003
TKAC, University of Minnesota
Proposed scheme of cerebral metabolism
BBB
BBB
pyruvate Lac
NAD+
NADH
Glccytosol
Glcplasma
TCA cycle
Lacplasma
CMRGlc
Lac efflux
CMRO2
Mitochondrion
malatemalate
Glu Glu
Asp Asp
2-OG 2-OG
OAA OAA
NAD+
NADH
H+
Mangia et al, J Cereb Blood Flow Metab 2007 TKAC, University of Minnesota
Nové progresívne metódy magnetickej rezonancie
Tkac, University of Minnesota
• neinvazivný charakter MR metód
• fMRI – mapovanie funkčných vlastností
• DTI/HARDI – mikroštruktúra mozgu
• MRS – neurochémia
Potenciál nových metód MR
Skvalitnenie medecinskej diagnostiky a terapie
Národné centrum NMR spektroskopie
NMR spektroskopia na Slovensku
Slovenská Technická Univerzita
Univerzita Komenského
Univerzita Pavla Jozefa Šafárika
Technická Univerzita Košice
Chemický Ústav SAV
Ústav Merania SAV
Univerzitná Nemocnica Ladislava Dérera
Tkac, University of Minnesota
V ramci štátneho programu budovania infraštruktúry – výrazná
investícia do modernizácie NMR pristrojovej techniky