A brief introduction to MR physicsA brief introduction to MR physics

Hydrogen/Proton: Hydrogen/Proton: A spinning topA spinning top

= = JJ

With and without the presence of an external With and without the presence of an external magnetic field (magnetic field (BB00)) in the z directionin the z direction

MM00

BB00zz

Randomly oriented hydrogenRandomly oriented hydrogenatoms (spins) in absence of anatoms (spins) in absence of anexternal magnetic fieldexternal magnetic field

The protons aligns with the external The protons aligns with the external field: Low field: 0.47 T, Clinical field: Low field: 0.47 T, Clinical fields: fields: BB00 = 1.5 – 3.0 T = 1.5 – 3.0 T

Together they create a macroscopicTogether they create a macroscopicmagnetic magnetic MM00 vector parallel with vector parallel with BB00

(and z)(and z)

Radio Frequency (RF) coils in the xy-plane (Radio Frequency (RF) coils in the xy-plane (BB11))

A 900 pulse flips M0 into

the xy-plane M0 aligns with the z-axis

BB11

RF on

An oscillating FID signal in the xy-plane (readout plane)An oscillating FID signal in the xy-plane (readout plane)

When the protons aligns with the external field again they When the protons aligns with the external field again they give up their energy to their surroundings. This signal is give up their energy to their surroundings. This signal is registered by a coil (like an antenna):registered by a coil (like an antenna):

RF off:RF off:The spins The spins relax back relax back to their to their equilibrium equilibrium state (along z)state (along z)

TT11 relaxation: relaxation:

The time it takes for The time it takes for MM00 to realign to realign

with with BB0 0 after the influence of after the influence of

an RF pulse. Dependent of the an RF pulse. Dependent of the exchange with the media. exchange with the media. TT1 1 is is

short for fat and long for watershort for fat and long for water

TT22 relaxation: relaxation:

The time it takes before the spinsThe time it takes before the spins(protons) reach equilibrium after (protons) reach equilibrium after spin-spin exchange and thereafter spin-spin exchange and thereafter dephasing in the xy-plane:dephasing in the xy-plane:TT22 TT1 1

The MR signal

• Intrinsic parameters: T1, T2, n(H)

• Instrument parameters: TR, TE

• Pulse sequences: vary TR and TE

• Contrast agents: manipulate T1 and T2

Contrast Agents (CA)

• Even though MR has high specificity, CA are often used to better visualize specific structures and pathology

• Indirect effect on hydrogen spins. The relaxation times (T1 and T2) are reduced, thus signal changes

• Either T1 or T2 CA’s, where T1 CA’s increase the signal and gives “positive” contrast, whereas T2 CA’s reduces the signal and gives “negative” contrast in the image

Different CA’s (exogenous)

Paramagnetic

• Positive contrast: n(H) increases, T1 reduces and T2 increases

• Much stronger T1 than T2 reducing effect, which in total gives an improved T1 contrast by the addition of paramagnetic agents

• T1-weighted images

• Some paramagnetic ions: Gd3+, Mn2+

Electron spin:• Non-paired electrons

MnMn2+2+11HH

ParamagneticParamagneticionion

• A magnetic moment analogous to the A magnetic moment analogous to the magnetic moment of protonsmagnetic moment of protons

• The magnetic moment of an electron ~600 times The magnetic moment of an electron ~600 times stronger than the magnetic moment of protons, and stronger than the magnetic moment of protons, and will therefore have an influence on themwill therefore have an influence on them

• Change the magnetic environment of the Change the magnetic environment of the protons, where Tprotons, where T11 and T and T22 will be reduced will be reduced

Efficacy in a homogenous solution

Relaxivity r1 and r2:

• The measured effectiveness of an CA to reduce T1 and T2

• Given in (s mM)-1

A simple linear formula:

T1 -1with CA = T1

-1without CA + r1 • [CA]

TT11 relaxation relaxation – – shorter and shorter Tshorter and shorter T1 1 (CA) (CA)

stronger and stronger signal in a Tstronger and stronger signal in a T1 1 weighted image where weighted image where

the CA is presentthe CA is present

Different types• Free metal ions are toxic in large quantities, that is why

they are bound to a chelate. This “shielding” influence the effectiveness of the CA, and safety is competing with efficacy

• Few side effects; does not result in severe allergic reactions as with X-ray CA’s

Extracellular (infarction, pathology)• Gd-DTPA (Magnevist*)Liver CA (pathology)• MnDPDP (Teslascan**)Intravascular/E.C. (few protons < 5% of all the tissue

protons). Large complexes which are trapped in the blood pool

• Gd-DTPA-BMA (Omniscan**)

Small moleculesSmall molecules

*Schering,**Amersham Health/GE Healthcare

Water Exchange Theory

H2OicH2Oic

t ec-1

t ic-1

ec: Extracellular

ic: Intracellular

Pic T1ic

Pec T1ec

Intrinsic values

A relaxivity in each ”homogenous” water compartment

Intracellular relaxivity: rIntracellular relaxivity: r1ic1ic

Monoexponential decayMonoexponential decayInversion Recovery pulse sequence:Inversion Recovery pulse sequence:

MMzz(t) = (t) = MM00 ( 1 - 2e ( 1 - 2e-t/-t/T1T1 ) )

T1-1

FAST EXCHANGE

1T’1ic

=1

T1ic

+1ic

1T’1ec

=1

T’1ec

+1ec

The apparent biexponential The apparent biexponential TT11’s are sums ’s are sums

of the intrinsic relaxation rates and of the intrinsic relaxation rates and the water exchange in each compartment:the water exchange in each compartment:

T’1ec

T’1ic

p’ic

p’ec

SLOW EXCHANGE: Apparent values

MMzz = = pp’’icic ( 1 - 2e ( 1 - 2e-t/-t/T1’icT1’ic ) + ) + pp’’ecec ( 1 - 2e ( 1 - 2e-t/-t/T1’ecT1’ec )) ))

Biexponential signal:Biexponential signal:

1/1/ = (PA)/V = (PA)/V

Intermediate exchange

2 SX equation for R1ic

2 SX equation for R1ec

2 SX equation for pic and pec

Calculating relaxivities, lifetimes of water and population fractions

EKSTRASTOFFEKSTRASTOFF

c (s)

temp

nonviscousliquids

viscousliquids Solids

R2

R1

1/T1M ,

1/T2M

SOLOMON-BLOEMBERGEN dipole-dipole term

20 MHz

60 MHz

100 MHz

10-11 10-7

CAec + 1H20ec

1H20ic

1H20*CAec

m-1

ic-1

ec-1

1H20*CAp CAp

1H20p

+

1H20ic

m-1

ic-1

p-1

Vessel wall

Interstitium

Intracellular

Ext

race

llula

r

Plasma

IntravascularE.C. Contrast Agent

Conclusions• Multi-component analyses of T1 and T2

revealed two compartments with different chemical environments in the heart cells detectable with 0.47 T MR

• Two compartment model more suitable for T1 analysis

• Close correlation between tissue Mn content and T1relaxation

• Slow water exchange in excised cardiac tissue

• Remarkably high relaxivity of intracellular Mn2+ ions

Main findings

MnCl2 Mn/Ca-100

-50

0

50

100

L

VD

P (

%)

-53

59

MnCl2 Mn/Ca0

1000

2000

3000

4000 3720

1620

Tis

sue

Mn

co

nte

nt

(nm

ol/

g d

ry w

t.)

Physiology and Mn contentPhysiology and Mn content

-100

-50

0

50

100

0

250

500

-70

-18 -9

468

269189

0.30 1.25 3.00 Ca2+ (mM):

LV

DP

(%

)

Mn

co

nte

nt

( n

mo

l/g

dry

wt.

)

25 µM MnCl2

-100

-50

0

50

100

0

500

1000

Ca2+ (mM): 0.30 1.25 3.00

-87-52 -52

574 556 692

LV

DP

(%

)

Mn

co

nte

nt

( n

mo

l/g

dry

wt.

)

100 µM MnCl2