12 medphys mri 5 - uni-heidelberg.de...spin-echo: contrast agent - intravenous injection of 0.1...

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RUPRECHT-KARLS-UNIVERSITY HEIDELBERG

Computer Assisted Clinical MedicineProf. Dr. Lothar Schad

12/9/2008 | Master‘s Program in Medical Physics

Chair in Computer Assisted Clinical MedicineFaculty of Medicine Mannheim University of HeidelbergTheodor-Kutzer-Ufer 1-3D-68167 Mannheim, GermanyLothar.Schad@MedMa.Uni-Heidelberg.dewww.ma.uni-heidelberg.de/inst/cbtm/ckm/

Physics of Imaging Systems

Basic Principles of Magnetic Resonance Imaging V

Prof. Dr. Lothar Schad



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Imaging Contrast

Imaging Contrast

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kx

k-space: after 1. TR k-space: after 2. TR k-space: after 256. TRky

Spin-Echo Sequence



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PwTR = 2775 ms

TE = 17 ms

T2wTR = 2775 msTE = 102 ms

T1wTR = 575 msTE = 14 ms

Spin-Echo Images

32143421factorT2

2TE/T

factorT1

1TR/TSE ]1[S

−

−

−

− ⋅−⋅= eeρ

- SE gold standard technique for T1 and T2 morphology

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12/9/2008 | Page 5

TR

TE

90

-

60ms

40

-

10ms

T1-weighted

T2-weighted

proton-weighted

300 - 800 ms 1500 - 3000 ms

no contrastSNR low

Spin-Echo Contrast: TR, TE



12/9/2008 | Page 6Spin-Echo: T1 Dependency

source: Reiser and Semmler. “Magnetresonanztomographie” 2002

T1-factor:[1-exp(-TR/T1)]

GM: T1 = 970 msWM: T1 = 600 ms

contrastBA

BA

SSSSC

+−

=

T1 - factor

WM

T1 - contrast

GM

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12/9/2008 | Page 7Spin-Echo: T2 Dependency

T2-factor:exp(-TE/T2)

GM: T2 = 110 msWM: T2 = 90 msT2 - factor

WM GM

T2 - contrast




12/9/2008 | Page 8Spin-Echo: TR, TE

source: Schlegel and Mahr. “3D Conformal Radiation Therapy: A Multimedia Introduction to Methods and Techniques" 2007

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12/9/2008 | Page 9Spin-Echo: TR, TE

SE contrast betweengrey and white matter



12/9/2008 | Page 10Spin-Echo: Multi-Slice

measurement #1

measurement #2

- interleaved SE measurement

- multi-slice SETR = 600 ms, TE = 10 ms→ about 60 slices can be measured

simultaneously !

1. slice

2. slice

3. slice

4. slice

5. slice

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12/9/2008 | Page 11Inversion Recovery Sequence

Mz

|Mz|




12/9/2008 | Page 12Inversion Recovery Images

321444 3444 21factorT2

TE/T2

factorT1

TR/T1TI/T1IR ]21[S

−

−

−

−− ⋅+−⋅= eeeρ

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12/9/2008 | Page 13Inversion Recovery Contrast

- WM and GM contrast dependency on TI, TR and TE- IR gold standard technique for T1 contrast


T1-contrast

T2-contrast

contrast [a.u.]

T2-contrast



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α

- example: α = 20° Mz - reduction by 6%Mxy- value 34% of Mz!!

M

x´,y´

z

Mz

Mxy

Gradient-Echo Sequence

spoiler

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12/9/2008 | Page 15

txGtdxGtx x

t

x ⋅⋅⋅−=⋅⋅−⋅= ∫ γγφ0

ˆ),(τ≤≤ t0

)(

ˆ),(

τγτγ

γγφτ

−⋅⋅⋅+⋅⋅⋅−=

⋅⋅⋅+⋅⋅⋅−= ∫txGxG

tdxGtxGtx

xx

t

xxττ 2≤≤ t

source: Liang and Lauterbur. “Principles of Magnetic Resonance Imaging” 2000

in rot. frame:

Gradient-Echo: Phase



12/9/2008 | Page 16Gradient-Echo: Steady-State

αcos1)1(MM TR/T1

TR/T10SS

z −

−

−−⋅

=e

enumber of RF

example: WMT1 ~ 600 msTR = 25 ms

*TE/T2SSzxy sinMMS −⋅=∝ eα

Mz steady-state:

Mxy steady-state:source: Reiser and Semmler. “Magnetresonanztomographie” 2002

dephasing oftransversal

magnetization

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12/9/2008 | Page 17Gradient-Echo: FLASH

Haase et al. JMR 1986

FLASH signal: 3214434421 actor*T2

*TE/T2

actorT1

1

1FLASH cosE1

sin)E1(Sf

f

e−

−

−

⋅−−

⋅=ααρ with E1 = exp(-TR/T1)

Ernst-angle: ( )TR/T1E arccos −= eα

FLASH: “fast low angle shot”

contrast [a.u.] contrast [a.u.]

T1-contrast

ρ-contrast



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SE GE

α = 90° / 180°TE = 20 ms

TR = 600 ms

Taq: minutes

α = 25°TE = 7 ms

TR = 20 ms

Taq: seconds !!

Gradient-Echo: Measuring Time

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12/9/2008 | Page 19Gradient-Echo: Examples I

spin-echoTR = 680 msTE = 15 msα = 90°

T1-contrast

3D FLASHTR = 60 msTE = 40 msα = 25°

T2*-contrast

2D FLASHTR = 170 ms

TE = 5 msα = 70°

T1-contrast

- no T2 contrast with gradient-echo technique !



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CT SETE = 20 ms

GETE = 20 ms

normal bone

osteoporosis

Gradient-Echo: Examples II

susceptibilityeffect

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12/9/2008 | Page 21Gradient-Echo: FISP

- FISP: “fast imaging with steady precession”- steady-state free precession sequence: SSFP- no spoiler, all phases are compensated- Mxy contributes to Mz→ more signal !- FISP signal for TR<<T1 and TR<<T2*:

Oppelt et al. Electromedica 1986

321444444 3444444 21 factor*T2

*TE/T2

factor*T1/T2

FISP cos)T1/T2*1(*T1/T21sinS

−

−

−

⋅⋅−++

⋅= eα

αρ

- FISP contrast: T1/T2*water: ~ 1, all other tissues: ~ 10

slice selection gradient

gradient-echo

phase encoding gradient

frequency encoding gradient



12/9/2008 | Page 22Gradient-Echo: FISP Problem

concept• transverse magnetization is not spoiled

(as in FLASH)• complete refocusing of all gradients in

one TR

problem• signal equation yields T1/T2 contrast• susceptibility differences can cause

artifacts• high flip angles (SAR)

solution• strong gradients• very short TR (< 5 ms)

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12/9/2008 | Page 23Gradient-Echo: FISP Contrast

- FISP sequence parameters:TR/TE/α = 2.6 ms / 1.4 ms / 55°⎟⎟

⎠

⎞⎜⎜⎝

⎛+−

=1*T1/T21*T1/T2arccosoptα



12/9/2008 | Page 24Gradient-Echo: Fat-Water Separation

- chemical shift between protons of water H2O and fatty tissue CH2 is about 3.5 ppm or 220 Hz at 1.5 T

- 1/220 Hz = 4.55 ms →TE = 4.55, 9.1 … ms fat / water: “in-phase”TE = 6.8, 11.4 … ms fat / water: “opposed-phase”

B0

90°

α

RF

S

fat water

W WFF

“in-phase” TE = 9.1 ms

“op.-phase” TE = 6.8 ms

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12/9/2008 | Page 25Spin-Echo: Fat-Suppression

- no fat-water separation possible since refocusing 180° pulse- preparation by frequency selective 90°-pulse to select only fat resonance (CHESS) and to destroy fat signal by spoiling

B0

90°180°

90°180°

RFS

fat water W

W

F

F

no fat-suppression with fat-suppression

x



12/9/2008 | Page 26Spin-Echo: Contrast Agent

- intravenous injection of 0.1 mmol/kg paramagnetic contrast agent Gd-DTPA- shortens locally T1 (ca. 1000 ms → 100 ms)- signal increase at SE imaging by a factor of 2 - 4 !- detects disruption of blood brain barrier → tumor grading !- also ferromagnetic nano-particles (SPIO ~ 100 nm, USPIO < 50 nm) available → liver

+

++

+

++

++

+

e-N S

Gd-DTPA complex

Gd

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12/9/2008 | Page 27

(by the different changes in relaxation times after their injection)

2. negative contrast agents- short T2 relaxation time - dark on MRI (decreased signal intensity)- small aggregates often termed superparamagnetic iron oxide(SPIO) and ultrasmall superparamagnetic iron oxides (USPIO) - crystalline iron oxide core and a shell of polymer (e.g. dextrane)

1. positive contrast agents- a reduction in the T1 relaxation time (increased signal intensity)- bright on MR images- small molecular weight compounds containing gadolinium, iron ormanganese

- unpaired electrons in their outer shells

Contrast Agent: Classification



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• good solubility in water • high thermodynamic and possibly kinetic stability to ensure against the in vivo release of toxic Gd3+ ions and free ligand molecules

• short T1 relaxation time

gadolinium:

• large magnetic moment • long electron spin relaxation time (~10-9 s at the magnetic field strengths of interest for MRI applications)

• optimum efficiency for nuclear spin relaxation of the interacting nuclei

Parker and Williams. J Chem Soc 1996 Aime et al. Chem Soc Rev 1998

Contrast Agent: Gd Requirements

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- all considered safe enough for clinical use

- octadentate ligands: one water molecule in the inner coordination sphere - rapid exchange with the bulk solvent to affect the relaxation of all solvent protons

Paul-Roth and Raymond. Inorg Chem 1995

Contrast Agent: Gd Ligands and Complexes



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Gadopentetate(Magnevist)

courtesy: Weinmann, Schering AG

Contrast Agent: Gd Spherical Models

Gadoterate(Dotarem)

Gadodiamide(Omniscan)

Gadoteridol(ProHance)

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• octadentate coordination of gadolinium

• one free coordination side is occupied by a water molecule

• relationships between the chemical structure and the factors determining the ability to enhance the water protons relaxation rates

• for a positive CA → short T1 time → high longitudinal relaxation rate

Contrast Agent: Gd-DTPA Complex



12/9/2008 | Page 32

dipolar interaction between the paramagnetic ion and the proton nuclei of coordinated water molecules

Bloemenbergen and Morgan. J Chem Phys 1961 Solomon. Phys Rev 1955

1. the number of metal bound water molecules q2. molecular reorientation time τR3. electron-spin relaxation time τS4. and chemical exchange time τM

described in detail by the Solomon-Bloembergen-Morgan theory

Gd-DTPA Relaxation Mechanism

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12/9/2008 | Page 33Spin-Echo: Gd-DTPA Example

SE T1w SE T2w SE T1w

- typical measuring protocol in brain diagnostics

intravenous injection of 0.1 mmol/kg Gd-DTPA

patient: glioblastoma



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Fast Imaging

Fast Imaging

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12/9/2008 | Page 35Fast Spin-Echo Imaging

Gs

Gp

Gr

RF90°

TEeff

1 total k-space line is acquired with every echo

signal-acquisition

180° 180° 180°

echo spacing

echo 1

echo 2

echo 3

signalfluid

muscle

time

- “turbo-SE-technique” (TSE) withacceleration-factor 3

- acquired k-space data afterfirst TR

compensation of Gp after signal acquisition

Hennig et al. MRM 1986



12/9/2008 | Page 36PSF: K-Space Inhomogeneity

k-space

15 echoesΔTE = 10 msT2 = 50 ms

position [pixel]

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12/9/2008 | Page 37Fast Spin-Echo Imaging: Examples

TSEturbo-factor: 3

TR / TE = 4 s / 11 msmatrix: 320 x 256

3:36 min

- tissue with long T2 (water) → sharp (see arrow)- tissue with short T2 (fat) → blurred

TSEturbo-factor: 33

TR / TE = 4 s / 11 msmatrix: 320 x 256

16 s TSE heartturbo-factor: 23ECG-triggered

breath hold



12/9/2008 | Page 38Fast Spin-Echo Imaging: FLAIR

- “turbo-inversion-recovery”-sequence (TIR) for fluid suppression followed by TSE readout

- “fluid-attenuated-inversion-recovery” (FLAIR)

- patient with brain tumourTSE: 4000/115 ms, TF = 15FLAIR: 9000/115 ms, TF = 21,

TI = 2500 ms

TSE FLAIR

TI

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12/9/2008 | Page 39Fast Spin-Echo Imaging: HASTE

- HASTE:“half-Fourier acquisitionsingle-shot turbo spin-echo”

- HASTE lung imaging:TE = 29 ms, ΔTE = 3.6 ms,N = 50 echoes, GRAPPA = 2,taq = 200 ms ! - lung parenchyma

is visible !

sequence

differenceimage

acquiredhologram

calculation ofmissing pointsby mirroring

at origin

reconstructedMR-image

k-space frequency encodingph

ase

enco

ding

Fourier transformation



12/9/2008 | Page 40

Mansfield and Pykett. JMR 1978

Fast Gradient-Echo Imaging: EPI

- “echo-planar imaging” EPI- multi-gradient imaging technique- single-shot technique with strong requirementsto the gradient power

- strong T2* dependency → susceptibility artifacts !- fastest imaging technique

Sir Mansfield2003 Nobel prize in medicine

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12/9/2008 | Page 41Fast Gradient-Echo Imaging: EPI Technique



12/9/2008 | Page 42EPI Problem: N/2 Ghosts

gradient echo EPI

echo shift ofodd againsteven echoes

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12/9/2008 | Page 43EPI Problem: Field Inhomogeneities

gradient echo EPI



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40 slices in 4 s !

Fast Gradient-Echo Imaging: EPI Examples

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classical EPI

Fast Gradient-Echo Imaging: EPI Methods

spin-echo EPISE-EPI

diffusion-weighted EPIDW-EPI



12/9/2008 | Page 46Fast Gradient-Echo Imaging: 3D FLASH

- whole brain imaging: 3D FLASH: 20/6/30°, 256 slices- 3D isotropic resolution: 1 x 1 x 1 mm3, taq ~ 20 minHaase et al. MRM 1986

measured

reconstructed

z

HF

G

G

G

x

y

AQ

Echo

TETR

Nslice

Nphase

N freq

Spin-dephasierung

3D-FLASH-Sequenz3D FLASH sequence

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12/9/2008 | Page 473D FLASH: Example

- high resolution heel imaging:- 3D FLASH: 25/11/30°, 100 slices, taq ~ 10 min - 3D isotropic resolution: 0.4 x 0.4 x 0.4 mm3 !!!

16201630164016501660167016801690170017101720173017401750176017701780179018001810

directionhorizontal vertical 45° 135°

run

leng

th n

onun

iform

ity- clinical application: osteoporosis



12/9/2008 | Page 48Fast Gradient-Echo Imaging: MP-RAGE

- MP-RAGE: 3D “magnetization prepared rapid gradient echo” technique

- volunteer whole brain imaging:MP-RAGE: 10/4/10°, TI = 200 ms, 128 slices

- 3D isotropic resolution: 0.9 x 0.9 x 1.2 mm3

taq ~ 8 min !Mugler and Brookeman. MRM 1990

TI

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12/9/2008 | Page 49Fast Gradient-Echo Imaging: PSIF

- PSIF: 3D reversed timing of FISP “noissecerp etats ydaets htiw gnigami

tsaf” technique - volunteer whole brain imaging:PSIF: 17/7/50°, 128 slices

- 3D “isotropic” resolution: 0.9 x 0.9 x 1.2 mm3

taq ~ 10 min !Bruder et al. MRM 1988

phase development excitation refocusing



12/9/2008 | Page 50Clinical Application: MP-RAGE, PSIF

Friedlinger et al. Comp Med Ima Graph 1995

- brain volumetry (GM, WM, CSF) in Alzheimer disease

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12/9/2008 | Page 51Clinical Application: 3D Visualization

- functional MRI overlaid to MP-RAGE - planning of neurosurgery



12/9/2008 | Page 52Fast Imaging: Hybrid Technique GRASE

- GRASE: “gradient and spin-echo” technique- TGSE: “turbo-gradient-spin-echo” technique- TSE technique mixed with GE’s- k-space variability: SE’s in center of k-space

GE’s at border of k-space

- volunteer high resolution imaging:GRASE: 2030/112/90° ms

- resolution: 0.4 x 0.4 x 2 mm3 !

Oshio and Feinberg. MRM 1991

spin-echo

gradient-echoes

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12/9/2008 | Page 53

conventional1 echo / TR

hybridmultiple echoes / TR

single-shotall echoes / TR

SEGE / FLASH

FLAIRMP-RAGE

FISPPSIF

TSETGSE / GRASE

HASTEEPI

Summary: K-Space Scan Options



12/9/2008 | Page 54Summary: K-Space / Speed

spin-echoes

gradient-echoes

spee

d

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12/9/2008 | Page 55Sequence Family



12/9/2008 | Page 56

FourierFourier--CodingCodingKK--SpaceSpace

CSECSE

IRIR

TIR, TIRM, TIR, TIRM, TFLAIRTFLAIRHASTEHASTE

TSE, FSETSE, FSERARERARE

GREGRE

FLASHFLASHSPGRSPGR

T1T1--FFEFFEspoiled FASTspoiled FAST

FISPFISPGRASSGRASS

FASTFASTT2T2--FFEFFE

trueFISPtrueFISPCISSCISS

DESSDESS

PSIFPSIFCECE--FASTFAST

turboFLASHturboFLASHsnapshotFLASHsnapshotFLASH

FSPGRFSPGRMPRAGEMPRAGE

EPIEPITGSETGSE

GSEGSEGRASEGRASE

© W. Nitz, Siemens AG

TIR

TGSE

FLASHTSE

PSIF

MPREPI

SESE GEGE

trueFISP

Sequence Family with Examples

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12/9/2008 | Page 57Babylonian Confusion of Tongues I

name also turbo-FLASH, TURBO-FFE, Snapshot-FLASH

GRE, fast FLASH with preparation pulse for contrast enhancement

Fast spoiled GRASSFSPGR

TSE, RARESE with multiple 180°-pulses, one raw data line per echoFast spin echoFSE

-SE with 180°-pulse at the beginning, long inversion time for fluid attenuation

Fluid attenuated inversion recovery

FLAIR

T1-FFE, Spoiled GRASSGRE with small angle excitationFast low angle shotFLASH

name also GRASS, FASTGRE using steady state magnetizationFast imaging with steady precession

FISP

FISPGRE with small angle excitationFast field echoFFE

name also FISP, FASTGRE using steady state magnetizationFast acquired steady state technique

FAST

multiple GRE after one excitation; mostly all raw data in one pulse train

Echo planar imagingEPI

double-GRE-sequence where GRE- and SE-parts are measured separately and added afterwards

Double echo steady stateDESS

two GRE-sequences with SE-part where single signals are added constructive

Constructive interference in steady state

CISS

name also PSIF, CE-FASTGRE with SE-part using steady state magnetizationContrast enhanced GRASSCE-GRASS

name also PSIF, CE-GRASS

GRE with SE-part using steady state magnetizationContrast enhanced FASTCE-FAST

SynonymsExplanationNameAcronym



12/9/2008 | Page 58Babylonian Confusion of Tongues II

SE-sequence with 180°-pulse at the beginning, imaging of absolute signal

Short TI inversion recoverySTIR

Pulse train with three 90°-pulsesStimulated echo acquisition mode

STEAM

name also FLASH, FFEGRE with small angle excitationSpoiled gradient refocused acquisition in the steady state

Spoiled GRASS

name also turbo-FLASH, FSPGR, TFE


Snapshot FLASHsnapshotFLASH

90°-180°-pulse trainSpin echoSE

name also TSE, FSESE with multiple 180°-pulses, one raw data line per echoRapid acquisition with relaxation enhancement

RARE

name also CE-FAST, CE-GRASS

GRE with SE-part using steady state magnetization“mirrored" FISPPSIF

FLASH, Spoiled GRASSGRE with small angle excitationT1 fast field echoT1-FFE

3D-variant of Turbo-FLASHMagnetization prepared rapid gradient echo

MP-RAGE

SE with 180°-pulse at the beginningInversion recoveryIR

Turbo-SE with Half-Fourier-Acquisition, all raw data in one pulse train

Half Fourier single shot turbo spin echo

HASTE

name also FISP, FASTGRE using steady state magnetizationGradient refocused acquisition in the steady state

GRASS

name also TGSETurbo-SE-sequence where SE is surrounded by GREGradient and spin echoGRASE

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12/9/2008 | Page 59Babylonian Confusion of Tongues III

name also Snapshot-FLASH, FSPGR; TFE


Turbo fast low angle shotTFL

name also turbo-FLASH, Snapshot-FLASH, FSPGR

GRE, with multiple 180°-pulses, one raw data line per echoTurbo fast field echoTFE

FSE, RARESE with multiple 180°-pulses, one raw data line per echoTurbo spin echoTSE

GE using steady state magnetization, all gradients are symmetric

True fast imaging with steady precession

trueFISP

Turbo-SE with 180°-pulse at the beginning, imaging of absolute signal

Turbo inversion recovery magnitude

TIRM

Turbo-SE with 180°-pulse at the beginningTurbo inversion recoveryTIR

name also GRASETurbo-SE-sequence where SE is surrounded by GRETurbo gradient spin echoTGSE

- the most important MRI-sequences !!SE / TSE

FLASH / FISP / EPI



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• best soft tissue contrast of allimaging modalities

• multi-planar slice orientation• no ionizing radiation• high flexibility of the method due to complex signal dependencyof physical parameters

It´s fun !!

MRI: Advantage - Disadvantage

• costs• availability• contraindication

- advantage - disadvantage

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12/9/2008 | Page 61

- essential prerequisites for MRI are:

1. nuclear spin (magnetic moment)

2. strong, homogeneous magnetic field (0.1 - 7 Tesla)

3. nuclear magnetic resonance(interaction of magnetization with a high frequency pulse)

4. relaxation (T1, T2)

Summary I



12/9/2008 | Page 62

ω = γ.B0• Larmor-frequency:

• magnetic field gradients for spatial encoding

- slice selection gradient- phase encoding gradient- frequency encoding gradient (readout gradient)

Summary II

ω(x) = γ.B (x) = γ.B0 + γ.Gx.x

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12/9/2008 | Page 63

• pulse sequences are a chronology of RF-pulses and gradients

• the most important basic types of sequences arespin-echo and gradient-echo sequences

• spin-echo sequences are using a 90°-pulse for excitation followedby a 180°-refocussing pulse

• gradient-echo sequences are much faster since they use flip-anglesof less than 90° for excitation without using any 180°-refocussing pulse

• EPI sequences are normally single-shot techniques, i.e. the completeimage is acquired after one RF excitation

Summary III



12/9/2008 | Page 64

• k-space formalism is a very helpful decription in MRI

kx = γ Gx t ky = γ Gy Tp

• the measured signals in MRI are the Fourier transformof the unknown image

( ) ( ) ( ) dydxeyxkkS ykxkiyx

yx +∞

∞−

∞

∞−∫ ∫= πρ 2,,

F.T.

Summary IV

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12/9/2008 | Page 65

source: Liang and Lauterbur. “Principles of Magnetic Resonance Imaging” 2000

Summary V



12/9/2008 | Page 66Finale

12 medphys mri 5 - uni-heidelberg.de...spin-echo: contrast agent - intravenous injection of 0.1...

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