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Part VI:Advanced Concepts (Selection)

Contents

Cardiovascular magnetic resonance imaging (CMR; cardiac MRI)

Diffusion Imaging(diffusion weighted imaging: DWI, diffusion tensor imaging: DTI)

BOLD (blood oxygenation level dependent) Imaging(functional MRI: fMRI)

MR Angiography (MRA)

MR Spectroscopy (MRS)

Cardiac Imaging

???

ECGECG

Non-invasive assessment of the function and structure of the cardiovascular system.(characterization of heart muscle as normal or abnormal: fat infiltration, oedematous,

iron loaded, acutely infarcted or fibrosed).

ECGECG--gatinggating ((„„prospectiveprospective gatinggating““): multiple ): multiple phasesphases

ECGECG

Segmentof k-space

phase5

Segmentof k-space

phase4

Segmentof k-space

phase3

Segmentof k-space

phase2

Segmentof k-space

phase1

Cardiac ImagingInitial attempts to image the heart were confounded by respiratory and cardiac motion, solved by

using cardiac ECG gating, faster scan techniques and breath hold imaging.

ECGECG--gatinggating ((„„prospectiveprospective gatinggating““): multiple ): multiple phasesphases

Example:GE-Sequence, TR = 10 ms, imaging matrix 128 x 128, heart beat rate 70/min

How long does patient has to hold his breath?

10 ms

ECGECG

Cardiac Imaging

Spins in motion: Diffusion

1 m

Molecular Diffusion of WaterDiffusion probes for dynamic displacements of water on cellular dimensions

and provides a unique insight into tissue structure, microstructure and organization.

1 0 00 1 00 0 1

D

D

In 1956, H.C. Torrey mathematically showed how the Bloch equations for magnetization would change with the addition of diffusion. Torrey modified Bloch's original description of transverse magnetization to include diffusion terms and the application of a spatially varying gradient. The Bloch-Torrey equation neglecting relaxation is:

Isotropic Diffusion

t

10 mT/m

-10 mT/m

t

v=0

with random motion (diffusion)

Diffusion (random walk) generates a randomphase offset after bipolar gradient:

Total signal is reduced depending on strengthof diffusion ands gradient

Diffusion Weighted Imaging (DWI)Diffusion-weighted imaging is an MRI method that produces in vivo magnetic resonance

images of biological tissues weighted with the local characteristics of water diffusion. DWI is a modification of regular MRI techniques, and is an approach which utilizes the

measurement of Brownian motion of molecules.

D: diffusion constant (water = 2.5x10-9m2/s), b: diffusion weighting factor (from gradients)

Example: G = 10 mT/m, = 30 msb ~130 s/mm2

S ~ 0.75 M0

Diffusion (random walk) generates a random phase offset after bipolar gradient

Diffusion Weighted Imaging (DWI)

2 3 223

b G

tG [m

T/m

]

0( , ) bDS b D M e

Signal attenuattion from diffusion:

t

2 2 21( )3

b G

G [m

T/m

]

Restricted Diffusion & Anisotropic Diffusion

Large compartements,high diffusion

cell

small compartements,low diffusion

Detection of affected regions afteracute stroke

Restricted Diffusion

0 00 00 0

DD

D

0 00 00 0

eff

eff

eff

DD

D

>

Nerve bundles: diffusion is higher along than across nerve fibres: Anisotropic diffusion!

Diffusion sensitizing gradients (Bx,Gy,Gz) can be applied independently along all three spatial directions (x,y,z)

This allows to calculate the direction of highest (lowest) diffusion within eachimaging voxel!

Anisotropic Diffusion

1

2

3

0 00 00 0

DD

D

Calculate eigenvectors!

fiber tracks in white matter

Diffusion Tensor Imaging: Tractography

Determine diffusion tensor from at least six measurements with diffusion sensitizing gradients along different directions.

Functional magnetic resonance imaging (fMRI)

Red blood cells containhemoglobine

Heme, part of hemoglobine, contains Iron (Fe)

Hemoglobine can either beparamagnetic or diamagnetic, depending on oxygenationstate

Heme group

hemoglobine

Functional magnetic resonance imaging is a type of specialized MRI scan used to measure the hemodynamic response (change in blood flow) related to neural activity in

the brain. It is one of the most recently developed forms of neuroimaging. Since the early 1990s, fMRI has come to dominate the brain mapping field due to its relatively low

invasiveness, absence of radiation exposure, and relatively wide availability.

Functional magnetic resonance imaging (fMRI)

Hemoglobine can either be paramagnetic or diamagnetic, depending on oxygenation state

magneticmoment

Deoxyhemoglobin

Fe

oo

no magneticmoment

Oxyhemoglobin

Fe

Magnetic field flux

vein

arterie

Functional magnetic resonance imaging (fMRI) BOLD: blood oxygenation level dependent imaging

0

frequency tTEdeox

0

frequency tTEox

Functional magnetic resonance imaging (fMRI) BOLD: blood oxygenation level dependent imaging

BOLD: blood oxygenation level dependent imaging

Firering nerve cells require energyEnergy is provided as oxygen and glucose via capilaries

This locally increases blood flowIncrease of blood flow exceeds demand of oxygen

This locally increases blood oxygenation

Functional magnetic resonance imaging (fMRI)

- normal flow- base level of [Hbr]- base level of CBV

HbO2Hbr

- increased flow- reduced level of [Hbr]- increased CBV

Activated stateResting stateArterioles

Capillaries

Venules

CBV=

cerebral blood volume

BOLD: blood oxygenation level dependent imaging

Functional magnetic resonance imaging (fMRI)

T2* (rest) < T2* (activation)

MR Angiography (MRA)

MRA: Introduction

Characterization of (Human) Vascular System

What is MRA used for?

MRA: Introduction

Vascular abnormalities for MRA?

• Stenosis• Aneurysm

• Arterial Venous Malformation (AVM)• Thrombus

• Plaque• Internal bleeding

• …

MRA: Properties of Blood

Arterial VenousT1 ~ 1200ms @ 1.5TT1 ~ 1500ms @ 3.0T

T1 ~ 1200ms @ 1.5TT1 ~ 1500ms @ 3.0T

T2 ~ 250ms T2 ~ 30ms

Flow Velocity (mean)

100 – 150 cm/sec (3.6 – 5.4 km/h) in abdominal aorta10 – 20 cm/sec (0.36 – 0.72 km/h) in peripheral arteries

Pulsatile: Peak arterial flow @ 150 – 200 ms afterventricular contraction

Relaxation Times

MRA: Techniques

Contrast Enhanced MRA (CE-MRA)

Non-Enhanced (native) MRA (native-MRA)

• high contrast-to-noise ratio (of course!)• fast acquisition dynamic imaging

• No flow induced dephasing of signal loss• Acquisition timing is important (bolus!)

• Gd related NSF is a concern

• can be quantitative• prone to artifacts

• techniques are region specific

CE-MRA

• became popular during 1995 – 1999

Requirements:• High resolution and coverage of large VOI

• Short acquisition times to allowbreath-holding, e.g. for visualization of

abdominal vasculature

Fast 3D Sequences 3D GRE!

CE-MRA: GRE Parameters

TRTE

TR: Repetition timeTE: Echo time: excitation (flip) angle

CE-MRA: GRE Contrast

What do we expect for a GRE acquisition

with short TR/TE (we want to be fast!!!)

and a 90° flip angle?

TR = 3ms << T1, TE ~ 0 ms, = 90°

CE-MRA: GRE Contrast

TR = 6 sec

TR = 3 msec

Signal of blood fora fast 3D GRE?

01(1 )TES S D EP

(1 0)

(1 1)

MRI: Contrast Agents (CA) revisited

2 2, 21/ 1/ [ ]nativT T CA r

Contrast enhancedMRI, cell tracking,SPIOs, USPIOs,…

1 1, 11/ 1/ [ ]nativT T CA r

Paramagnetic agents:

CA

Positive CA:low concentrated Gd-chelates. Predominantly reduction in T1 (electron-proton dipolar coupling).

Positive contrast in T1w-image!

Contrast agents accelerate T1 & T2.

CE-MRA

Gd contrast agents decrease T1 and thereby increase CNR between blood and soft tissue

CE-MRA

TR = 3.54 msTE = 1.38 ms

Flip = 25°1.0 x 1.0 x 0.9 mm

RF spoiled SSFP-FID(FLASH, SPRG, T1-FFE)

heavily T1-weighted

The contrast medium is injected into a vein, and images are acquired during the first pass (bolus) of the agent through the arteries.

This is the most common MRA method

Visualization:

Images (source is 3D) are displayed as 2D MIPs

(screen is 2D)

12 sec4 sec 16 sec 20 sec 24 sec8 sec 28 sec 32 sec

MRA: MIPs

MIP imaging was invented for use in Nuclear Medicine by Jerold Wallis, MD, in 1988

Maximum Intensity Projection

The highest intensity signal along each ray of is mapped onto the projection image

Cou

rtesy

of S

. Wet

zel,

Uni

vers

ity H

ospi

tal B

asel

Time-of-Flight (TOF) MRA

Remember: This is a native MRA technique!There is no contrast agent

…slice being imaged

TOF-MRA: Principle

Remember: This is a native MRA technique!There is no contrast agent

Short TR! SATURATION!

NO SIGNAL FROM TISSUE!

TOF-MRA: Principle

flow velocitystatic slow fast

saturationmaximum medium minimum

The effective T1 is reduced due to inflow

TOF-MRA: Principle

Inflow of venous blood

Elimination of venous signal?

TOF-MRA: Principle

flow velocitystatic slow fast

saturationmaximum medium minimum

saturated venous phase!

TOF-MRA (2D, 3D)

Inflow(flow-related enhancement)

Seqential 2D

MIP

Inflow related transient signal

Saturated background

RF spoiled SSFP-FID(FLASH, SPRG, T1-FFE)

(native) MR Angiography

TR ~ 50 msTE ~ 10 ms

Flip = 25

CE-MRA & TOF-MRA: Issues

The same sequence (FLASH) is used for TOF and CE-MRA and images rely on high CNR between blood and tissue (hyperintensesignal from blood):

Thus, the absence or reduction of the bloodsignal is related to the presence of somedisease…

Artifactual Signal Loss

2D-TOF/3D-TOF CE-MRA

• In-plane, slow or retrograde flow• Intravoxel dephasing (turbulent

flow, e.g., after stenosis)

• Improper bolus timing• T2* dephasing

Phase Contrast (PC) MRA

+=

variabel

transverse magnetization

M stationary

longitudinal magnetization

Signal Amplitude

Signal Phase

+

Amplitude Image

Phase Image

=

( )

( )

z z

z

v t G t dt

venct G t dt

Gra

dien

t fie

ldst

reng

th

Gradient waveform over time:

z

t

PC-MRA: PrincipleP

hase

imag

es m

easu

re th

e ve

loci

ty!

static

flow

+

φ

PC-MRA

TR ~ 50 msTE ~ 10 msFlip = 25°

flow encoding gradients

phase contrast MRAflow quantification

flow encoded(phase contrast)

RF spoiled SSFP-FID(FLASH, SPRG, T1-FFE)

Courtesy of F. Santini, Radiological Physics,Basel

3D PC MRA

PC-MRA

Courtesy of F. Santini, Radiological Physics,Basel

PC-MRA: Issues

• slow method: 1D: 1 flow, 1 reference, 3D: 3 flow, 1 reference

• long acquisition time (time for PC-MRA >> TOF-MRA)

• phase wraps & poor SNR: proper venc selection

• intravoxel dephasing:turbulent flow, diffusion, longer TE from flow-encoding

The strength of the PC-MRA technique is that in addition to imaging the

flowing blood, quantitative measurements of blood

flow occur at the same time.

MR Spectroscopy (MRS)

In Bloch’s classical description of the phenomenon, polarized nuclei precess about the direction of the main magnetic

field B0 with a frequency that is a product of the gyromagnetic ratio of the nucleus and the strength of the magnetic field at the nucleus B:

Nuclear Magnetic Resonance (NMR)

MRS and MRI arise from the same principle, nuclear magnetic resonance NMR,

first observed by Bloch and Purcell in 1946.

Larmor Equation:

: Larmor frequency, i.e., the resonance frequency: gyromagnetic ratio

In principle, all nuclei with show nuclear magnetic resonance.High natural abundance required to result in sufficient NMR signal.

Biological tissue: 1H is most abundant in water and fat.

Nuclear Magnetic Resonance (NMR)

Nuclear Magnetic Resonance (NMR)

Changes in the resonant frequency gives rise to the information content of both MRI and MRS!

In MRI, the resonant frequency is modified by gradients G imposed on the main magnetic field B0.

The frequency thus becomes a function of the position r and in this way, spatial information is extracted and images are created.

Introduction: Spectroscopy (MRS)

The origin of MRS dates to 1951 when Albert described small changes in resonant frequency of protons due to the local chemical

bonding environment. (protons are shielded from the full applied magnetic field Bo by surrounding electrons)

where the shift imparted by the local bonding environment is given the symbol and is called the chemical shift.

The frequency of resonance of a nuclei in a molecule is given by

In MRS, the resonance offset is normalized to the operating frequency of the magnet and further referenced to a standard to minimize confusion when comparing results from laboratories

using different field strengths.

Resonance positions are then reported in parts per million (ppm)

Introduction: Spectroscopy (MRS)

Electronegative atoms such as oxygen (O) or chlorine (Cl) attract electrons and cause deshielding of nearby hydrogen.

Each type of hydrogen has a unique position of absorption (called the chemical shift) in the NMR spectrum

Introduction: Spectroscopy (MRS)

Based on this standard, protons in water resonate at 4.8 ppm

regardless of magnetic field strength.

OH

H

C C C CH H H H

H H H H

0

3.5 ppm

H2O

Fat

[ppm]1.34.8

1 ppm = 64Hz @ 1.5 T1 ppm = 128Hz @ 3.0 T1 ppm = 298Hz @ 7.0 T

For 1H spectroscopy, the standard is the methyl proton resonance of

tetramethyl silane which was chosen to be 0 ppm.

The resonance of the methyleneprotons in adipose tissue is 1.3 ppm.

The shift between water and fat remains 3.5 ppm, regardless of field

strength, although the frequency difference in hertz changes!

Theoretical Background: Fourier Transform

Water and Fat generate a…

water: Aw

fat: Af

exp( 2iw t )

exp( 2if t )

…time varying signal response S(t):

Awexp(2iw t ) + Af exp(2if t )

…a time varying signal response: S(t)=Awexp(2iw t ) + Af exp(2if t )

21( ) ( )2

i vtF v S t e dt

…and its Fourier transform:

0

3.5 ppm

[ppm]1.34.8

Aw

Af

Theoretical Background: Fourier Transform

The „peak height“ in the spectrum relates to the amplitude

Theoretical Background: Line-Width

FFT

ppm0…

dirac-delta function (-0)

……ppm0

FFT~ T2

FWHMLorentzian function

……

Shifted Lorentzian functiondamped decay

x

=

=

ppm0

FFT

The „area under the peak“ in the spectrum relates to the amplitude

Theoretical Background: Line-Width

……damped decay

FFT

phase

oscillation

damping

Go for the real part of the Fourier transform of the signal!

FFT

Theoretical Background: Phase Shifting

However, proper phasing of the FFT signal is required

Theoretical Background: Truncation

*0 2

0

0

2 / , ( ) ~0 ,

i t t Tie e e t ts tt t

… …

Be aware: Truncation of the signal may cause

Fourier wiggles!

truncated damped decay

A filter (exponential envelope) can be appliedto smooth the truncation

(which removes thewiggles but not withoutbroadening the line).

Theoretical Background: Line Broadening

The main magnetic field B0 isperturbed by local susceptibility

changes on the macroscopic(e.g., air/bone – tissue interface), mesoscopic (e.g., vessels) and

microsopic (e.g., cells) level.

For brain @ 1.5T (64MHz), macroscopic susceptibility effectsinduce frequency changes in the

range of 30Hz ~ 0.5 ppm.

Macroscopic susceptibility effectscan be reduced by proper

shimming!

Proper and accurate shimming of the ROI is elementary!

ppm

Frequencydistribution ()

causingline-broadening

0 ppm

CA CB O H

H

H

H

H

H

Theoretical Background: J-Coupling

[ppm]

…fully decoupled

With increasing B0, the dispersion (difference in resonance frequency

in Hertz) between singletresonances increases linearly.

Closely spaced singlets become thus more distinct with increasing B0 (although the difference in ppm

remains the same.

[ppm]

…coupled

1 3 3 11 2 1

However, many of these resonances are not singlets (i.e., a single

resonance line), but multiplets.

Nuclei with different chemical shifts may exchange energy through the

bonding electron clouds in the molecule (J-coupling, being

independent on B0).

Theoretical Background: Summary

The Fourier transform relates the time-domain with the frequency domainand thus the decay of the signal with T2 relates to the line-width

(Lorentzian with FWHM ~ 1/T2)

Only the real part of the spectrum is used(less line broadening, but requires proper phasing)

A dispersion in resonance frequencies, e.g., induced by localsusceptibility changes, causes a broadening of the lines.

(proper shimming required)

Truncation of the FID may induce Fourier wiggles(can be removed by filtering, but broadens the line)

J-coupling may induce the appearance of multiplets(J-coupling is independent on B0, thus multiplets appear closer with increasing fields)

Separation of lines improves with increasing field strength(T2 ~ 100ms 0.050ppm @ 1.5T, 0.025ppm @ 3.0T, 0.011 @ 7.0T)

1H and X-nuclei Spectroscopy

MRS methods can be broadly classified into two categories:

1H MRS X-nuclei MRS

The dominant clinical application is 1H MRS,

since no additional hardware is required.(The same RF coils transmit and receive systems used for MRI are

also applicable to 1H MRS)

Imaging (H2O)

1 x 1 x 1 mm3

SNR ~ 100

MRS (NAA)

13 x 13 x 13 mm3

SNR ~ 100

[H2O] : [NAA] = 72 : 0.03 (Molar)

SNRH2O : SNRNAA 133 : 1

1H Spectroscopy: Sensitivity

…the problem with the water…

The dispersion of the 1H spectrum is small, with all the resonances of interest in the human within 5 ppm of the

water resonance (0 – 4.8 ppm).

The line shape of the water resonance in vivo yields a large base line signal,

overwhelming the resonances of interest.

RememberSNRH2O : SNRNAA 133 : 1

Water suppression required!Baseline correction required!

Sample of a 1H spectrum

4 3 2 1 ppm

PCr

GABA

GABA

Ala

Lac

Glc

PE

GSHGSHCr

Asp

MM

Cr + PCr

NAA

NAA

Glu GluGln

Gln

myo- Ins

GluGln Cho

scyllo-Ins

myo-Ins

Tau

High-resolution proton spectroscopy at 9.4 TAfter: Accurate Shimming

Water suppresionBaseline correctionPhase correction

1H Spectroscopy: Single Voxel Excitation

How can we select a small volume (~1 cm3)?

Localizedvolume

Methods:PRESS = Point-resolved spectroscopySTEAM = Stimulated echo acquisition mode

1H Spectroscopy: Localization Methods

A slice-selective 90o and two slice-selective 180° pulses form a spin echo from a single voxel.

Point-resolved spectroscopy: PRESSAchieves localization within a single acquisition

1H Spectroscopy: Localization Methods

TE/2

90° 90° 90°

TE/2TM

RF

Gx

Gy

Gz

Three slice-selective 90o pulses form a stimulated echo from a single voxel.

Only half of the available signal is obtained

Can achieve shorter TE than PRESS

Stimulated echo acquisition mode: STEAMAchieves localization within a single acquisition

2D-1H Spectroscopy: Chemical Shift Imaging

Chemical Shift Imaging (CSI)

Similar to MRI. The FID of a single voxel (i.e., its 1D-1H spectrum) is encoded with a phase (via gradients). Thisencoding has to be donealong every direction.

Thus, for a 32x32 imagingmatrix 1024 phase-encoded1D-1H-spectra are recorded…

The same principles apply as with 1D-1H MRS…

1H Spectroscopy: Summary

4 3 2 ppm

1

9

8

5

4

3

12,13

1717

6,7,182

10

1,2

16

16

6

6,77

20

14,15

2111,20

19

Energy metabolism:1: phosphcreatine (PCr)2: creatine (Cr)3: glucose (Glc)4: lactate (Lac)5: alanine (Ala)

Neurotransmission:6: glutamate (Glu)7: glutamine (Gln)8: GABA9: N-acetyl-aspartyl-glutamate (NAAG)10: aspartate (Asp)11: glycine (Gly)12: serine (Ser)

Membrane metabolism:13: phospho-ethanolamine (PE)14: phosphocholine (PC)15: glycerophosphocholine (GPC)16: N-acetyl-aspartate (NAA)

Antioxidants/osmolytes:17: glutathione (GSH)18: vitamin C (Asc)19: taurine (Tau)20: myo-inositol (Ins)21: scyllo-inositol (s-Ins)

1