Magnetická rezonancia Pohľad do mozgu - vedatechnika.sk · Magnetická rezonancia Pohľad do mozgu Ivan Tkáč Center for Magnetic Resonance Research U NIVERSITY OF M INNESOTA Tkac,

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


• 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)


• 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)


• prvé dva MR tomografy na Slovensku – Bratislava, Dérerova

nemocnica na Kramároch – (1992)

Magnetic Resonance Imaging (MRI)



Funkčná magnetická rezonancia

• základné princípy funkčného zobrazovania

• príklady

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

Základný princíp fMRI


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


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


izotropná difúzia

anizotropná difúzia

nervové vlákno (axon)

difúzny tenzor


Princíp difúzneho váženia

RF

90o ACQ

Gdif

čas


Princíp difúzneho váženia

RF

90o ACQ

Gdif

difúzia

čas

ADC

FA

SAV1

PA

LA

Diffusion Tensor Imaging (DTI)


High Order Diffusion Models: Q-Ball Imaging


Tractography using Higher Order Models


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


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


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


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


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


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


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


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


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


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


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


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


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


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

•••


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)


ppm02345678 1

Summed spectra from all subjects and both

stimulation paradigms

resting period

NT = 1536

FT, no weighting

difference

visual stimulation

x 20


+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


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


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+


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

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


V ramci štátneho programu budovania infraštruktúry – výrazná

investícia do modernizácie NMR pristrojovej techniky

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