ARTERIAL SPIN LABELING (ASL) - Universitetet i · PDF file1 ARTERIAL SPIN LABELING (ASL)...

1

ARTERIAL SPIN LABELING (ASL)

Matthias van Osch, Associate Professor

C.J. Gorter Center for high field MRI, Dpt of RadiologyLeiden University Medical Center

The Netherlands

223 October 2013Quantification of ASL 2

Contents

• Introduction on perfusion

• Acute stroke, reactivity, flow territory mapping

• Introduction of arterial spin labeling MRI

• Pulse-sequences

• Image readout

• Background surpression

• Quantification

• (Flow territory mapping) (probably too little time)

3

Gray matter

White matter

Microvasculature

Cast of cerebral human vasculature

2

4

Perfusion

Cerebral blood flow

amount of blood that enters the microvasculature per

secondml blood / min / 100 ml tissue

5Wednesday, October 23, 2013Arterial spin labeling 5

How can we measure perfusion?

• Exogenous contrast agents (next presentation)

Inject a bolus contrast agent and monitor dynamically the

concentration of the contrast agent in brain tissue,

microvasculature and arteries

Dynamic susceptibility contrast MRI (DSC-MRI) or

bolustracking MRI

Positron emission tomography (PET)

CT perfusion (CTP)

• Endogenous contrast agents

Label the blood magnetically and monitor the inflow

Arterial spin labeling (ASL)

6

Acute stroke

• Identifying the perfusion/diffusion mismatch (“penumbra”?)

48-year old woman presenting within 6 hours after symptom onset

Bokkers, Hernandez, Merino, Mirasol, van Osch, Hendrikse, Warach, Latour: Stroke. 2012 May;43(5):1290-4

3

7

66-year old woman presenting within 1 hour after symptom onset


Acute stroke

8

Acute stroke

DSC (n = 64)

ASL Yes No

Yes 32 4

No 7 21

Perfusion deficits

Interrater agreement

• DSC: 0.64

• ASL: 0.6


DSC (n = 64)

ASL Yes No

Yes 18 6

No 2 38

Significant perf / diff mismatch

Interrater agreement

• DSC: 0.74

• ASL: 0.51

9

ASL false negative for perfusion deficits in 7 patients

•5 cortical gray matter, in 4 ASL of poor quality

•2 lesions in the basal ganglia

ASL false positive for perfusion deficits in 4 patients

•3 of the DSC images were poor quality

In the 30 cases where DSC was not performed

•11 patients had clinically confirmed stroke

•ASL detected 6 perfusion deficits, 3 significant mismatches

Acute stroke

4

10

ASL in Alzheimer’s Disease

Alzheimer’s Control

Axial Sagittal Coronal

In collaboration with:UT Southwest, Dallas, USA

Yezhuvath US, Uh J, Cheng Y, Martin-Cook K, Weiner M, Diaz-Arrastia R, van Osch M, Lu H. Neurobiol Aging. 2012 Jan;33(1):75-82Forebrain-dominant deficit in cerebrovascular reactivity in Alzheimer's disease.

11Wednesday, October 23, 2013Visit Philips LUMC 11

Brain tumor (Glioblastoma multiforme)

ASL DSC-MRI

Scanned by technicians, post-processing on the console

12Wednesday, October 23, 201312

Vasodilatory capacity (Acetazolamide)

5


Vasodilatory capacity

Advantage of perfusion MRI: Reactivity in sub-regions, e.g. hypertensive SVD versus CAA

14Wednesday, October 23, 2013Visit Philips LUMC 14

Pharmacological MRI


Superselective ASL:labeling of single small arteries

In collaboration with Kiel

2 cm

Tuneable labeling spot with effective labeling thickness of only 1-2 cm

6

16

Arterio-venous malformation

Wednesday, October 23, 2013LIBC 16

http://www.avmsurgeon.com/aboutavms.html ASL angiography


Patient with Arterio-Venous-Malformation

• 48yo ♂ patient, symptomatic AVM (severe headaches)




Selective ASL of major brain feeding arteries did not provide the requested information:

• ICA right• ICA left• BA




7


AVM

AVM AVM

Ø = 2.1 mm

Ø = 3.0 mm

TOF-MIP

ASL pre-surgery

Superselective ASL performed exclusively on feeding vessels of the AVM.

T1w





Ø = 1.2 mm

Ø = 2.1 mm

T1w

ASL post-surgery

TOF-MIP

Superselective ASL performed on remained vessels (former feeding vessels of the AVM).





T1w

ASL pre-surgery

ASL post-surgery

fMRI (language)

Temporal speech disorders of the patient after surgery.

Parts of Wernicke‘s area supplied by former feeding vessels of AVM (proved by fMRI).

2.

Changes of the territorial distribution of cerebral perfusion 24h after surgery.

Decreased steal effect after removal of AVM.

1.




8

22

ASL in Meningeoma 3T 02/2011Patient 1

23

ASL in Meningeoma 3T 02/2011Patient 1

24

ASL in Meningeoma3T 06.10.2011

TOF TOF MIP

Patient 1

9

25

T2

ICA ri + le

global

ICA + Menigia Media left

Patient 1

26

T1 CE

T1 CE

10/2011

02/2011

Patient 1

27

Principle of arterial spin labeling

• ASL is based on tracer kinetics to

measure blood flow, similar to the

nitrous oxide method, perfusion

CT and DSC-MRI

• Use blood as a tracer by inverting

its longitudinal relaxation: NO

CONTRAST AGENT

• Half-time of tracer governed by

the longitudinal relaxation time

• Freely diffusing tracer:

accumulation of tracer reflects

blood flow

Kety, S. S., and C. F. Schmidt. The nitrous oxide method for the quantitative determination of cerebral blood flow in man:

theory, procedure, and normal values. J. Clin. Invest. 27: 107–119, 1948.

10



Spatial selective inversion



Spatial selective inversion


Label

Control


-Spatial selective inversion

30×

11



Slab selective inversion pulse Adiabatic inversion plane

Pulsed Labeling (PASL)Continuous Labeling (CASL)Pseudo continuous (pCASL)


Timing differences between PASL and CASL

33

Half-time of tracer

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9

Time (s)

Sig

nal (

%)

The labeled spins decay with the longitudinal relaxation time T1

(T1,blood≈1650 ms @ 3Tesla)

16%

12


•Transport time to imaging slice is

approximately 1 sec

•Probably takes another 1-1.5 s to

reach capillary bed

pCASL

PASL

Arrival-time of label

1-3 s


Arrival-time of label vs decay of tracer

pCASL

PASL

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9

Time (s)

Signa

l (%

)

Wait long for arrival of spins in microvasculatureImage as quickly possible due to loss of label

1-3 s

36

Loss of label: longitudinal relaxation

100 ms 300 ms 600 ms 1000 ms 1500 ms 2100 ms 2600 ms 3000 ms 3500 ms

Inflow of label Decay of label



Angiogram Perfusion Noise

13

37

Problem in patients: delayed arrival

100 ms 300 ms 600 ms 1000 ms 1500 ms 2100 ms 2600 ms 3000 ms 3500 ms

Inflow of label Decay of label



Angiogram Perfusion Noise

MIP (merged)

MIP (ICA right)

MIP (ICA left)

MIP (BA)

MIP (TOF)

Example of ASL angiographyDelay = 400 ms

Example of ASL perfusion imagingDelay =1650 ms

14

Magnetization transfer effect

• Macromoleculeshave much broader resonance frequency spectrum than water, but the influence of RF-pulses is transferred to the larger free water pool

• When RF-power between label and control differs than this can result in a non-CBF related signal difference

PASL-TILT (Pruessman/Golay)

Label

Control

slice selectiveinversion

acquisition

acquisition

+90°

acquisition

acquisition

+90°

+90° -90°

PASL-FAIR (Kim)

Label

Control

slice selectiveinversion

Non-selectiveinversion

acquisition

acquisition

acquisition

acquisition

180°

180ºVenous label

15

Continuous ASL: single slice (Williams)

Label

Control

Inversion plane

Inversion planeAbove imaging

acquisition

acquisition

acquisition

acquisition

Pseudo continuous ASL

• Pseudo continuous ASL1

• Comparable to CASL

• Create a label bolus with a fixed duration of approx. 1.5 sec

• No continuous RF, therefore it is possible to use the body

transmit coil

• Use of a train of RF-pulses of 0.5 ms with 0.5 ms interval

1Garcia and Alsop, ISMRM 2005Labeling (1650 pulses)

Grz

RF

Steady-state for a series of RF-pulses

Garcia and Alsop, ISMRM 2005

16

Manipulation of static state

Phase difference between RF and spins determines the steady state

1. By changing the phase of the RF pulses we can manipulate the

steady state

2. By changing the phase of the spins we can manipulate the steady

state

Phase change ∝ Gradient strength * x * ∆t

Magnetic field ~ rotating speed of spins

Gradientstrength


Between 2 RF pulses there is an extra gradient to create flow induced phase differences that takes the magnetization towards inversion

Gradient Phase

Gr z


With a correct

change in phase the

magnetization is

tipped to inversion

17


Label

Grz

RF

Control

Grz

RF

Control situation

Control

Grz

RF


delay

(p)CASL or PASL?

delay(p)CASL

0 sec 1 sec 2 sec 3 sec

PASL

0 sec 1 sec 2 sec 3 sec 4 sec?

18


delay

(p)CASL or PASL?

delay(p)CASL


PASL

0 sec 1 sec 2 sec 3 sec 4 sec

FasterMore averages


delay

(p)CASL or PASL?

delay(p)CASL


PASL


1.5-2 sec of label

Spatial label, but how long in time?


Input function in PASL

For PASL a large part of the vasculature is labeled. The amount of labeled spins is dependent on the volume of the arteries in the labeling plane (e.g. curved vessels, collateral pathways, etc).

Will be different for different vessels (especially anterior vs posterior)

19


delay

(p)CASL or PASL?

delay(p)CASL


PASL


1.5-2 sec of label

~500-800ms+ uncertainty!

SNR ×2declared“workhorse”

56

Recommendation for labeling approach

23 October 2013Quantification of ASL 56pCASL labeling

57

Readout of ASL

• The goal is to measure the amount of label, i.e. inverted spins

• Therefore, we need proton-density weighted sequence

• The label will decay with the T1 of blood/tissue and we are only allowed to start scanning after a sufficient delay to allow the label to reach the microvasculature: fast imaging

• ASL is a tiny signal: voxel size factor 10-50 smaller than anatomical imaging

• Requirements:

• Short echo-time

• Short readout (<300 ms)

• Whole brain coverage

• Single shot EPI

• Spiral (difficult)

• Single shot 3D (GRASE)

• Segmented 3D sequences

20

58

slice 3slice 2slice 1

58

2D Echo Planar Imaging, cartesian

Gent, 02-04-2010

• Readily available on most scanners

• Single shot � 1 slice per excitation, ~ 25 ms per slice

Gslice

RF

Gphase

Gread

Acq.

5959

3D GRASE

Gent, 02-04-2010

• Enables single shot whole brain imaging

• Relatively high signal to noise

• Blurring in slice encode direction

Gslice

RF

Gphase

Gread

Acq.


Background suppression

• ASL is a subtraction technique

Static tissue Static tissueLabeled spins

• Due to movements, and respiratory and cardiac noise the

static tissue can show large signal variations

• Use background suppression to minimize noise

21

6161

-1

-0.5

0

0.5

1

0 1000 2000 3000 4000

time (msec)

MZ

GM

-1

-0.5

0

0.5

1

0 1000 2000 3000 4000

time (msec)

MZ

GM

BStiming

satinv

Background suppression, principles

Arterial spin labeling

3200 ms

pCASL

-1

-0.5

0

0.5

1

0 1000 2000 3000 4000

time (msec)

MZ

GMWM

-1

-0.5

0

0.5

1

0 1000 2000 3000 4000

time (msec)

MZ

GMWMCSF

Reminder 1

Do not affect label

• Saturation is spatially selective on brain

• Inversion is global

Reminder 2

• BS affects different tissues equally

6262

BStiming

satinv



Reminder 1

Do not affect label

• Saturation is spatially selective on brain

• Inversion is global

3200 ms

pCASL

-1

-0.5

0

0.5

1

0 1000 2000 3000 4000

time (msec)

MZ

GMWMCSF

Reminder 3

Equal sign for all tissues

• If not: intra voxel cancellation

Reminder 2

• BS affects different tissues equally

6363

-1

-0.5

0

0.5

1

0 1000 2000 3000 4000

time (msec)

MZ

GM



3200 ms

pCASL

-1

-0.5

0

0.5

1

0 1000 2000 3000 4000

time (msec)

MZ

GMWM

-1

-0.5

0

0.5

1

0 1000 2000 3000 4000

time (msec)

MZ

GMWMCSF

BStiming

satinv1 inv2

Reminder 4

BS affects tissues equally

• To null more tissues, more inversion pulses are needed

22

6464

BS and signal changes


-1

-0.5

0

0.5

1

MZ

GM

WM

CSF

6565

-0.5

0

0.5

time (msec)

MZ

GM

WM

CSF

Timing in Background Suppression


Reminder 5

• 2D imaging gives decrease of BS in subsequent slices

• effect on 3D less severe

66

-0.5

0

0.5

time (msec)

MZ

GM

WM

CSF

Timing in Background Suppression

Reminder 5

• 2D imaging gives decrease of BS in subsequent slices

• effect on 3D less severe

2D-EPI

23

67

Basics of quantification

• Correct for efficiency of

labeling

• Assume all label has arrived in

the imaging voxel

• Correct for loss of label due to

T1-relaxation

• Relate signal towards a

reference value, i.e. signal

within a voxel containing

100% arterial blood or a

proton density weighted scan

Wednesday, October 23, 2013Perfusion and permeability 67Arterial spin labeling

68

What is recommended?

23 October 2013Quantification of ASL 68Quantification of ASLArterial spin labeling

69

White paper recommendation


24

70



71



72

Recommendation


Conversion to ml/100ml/min ∆M (ASL-signal)

ASL is based on inversion

Labeling efficiencyM0: reference for arbitrary scaling of signal intensities in MRI: proton density scan corrected for difference in proton content between water and tissue

Quantification of ASLArterial spin labeling

25

73

Recommendation


�

��

��,��

��,��

�

��,��

=

��,��

�

��,��

��

��,��

Quantification of ASL

74

Half-time of tracer

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9

Time (s)

Sig

nal (

%)



16%


75

Recommendation


�

��

��,��

��,��

�

��,��

=

��,��

�

��,��

��

��,��

Quantification of ASL

labeling imagingPLD

T1-relaxation


26


Labeling efficiency of PASL

• Check inversion effeciency and profile in phantoms

• Redo these experiments in vivo, because B1-distribution is different in vivo than in phantoms

• Acquire images at different delay times (inversion recovery)



Remember: switch off pre-saturation pulses and post-labeling saturation

0

50

100

150

200

250

300

0 200 400 600 800 1000 1200 1400 1600

Inversion time (ms)

MR

-sig

nal (

a.u.

)

kl



Remember: switch off pre-saturation pulses and post-labeling saturationRemember: modulus data rectifies noise

0

50

100

150

200

250

300

0 200 400 600 800 1000 1200 1400 1600

Inversion time (ms)

MR

-sig

nal (

a.u.

)

kl

27



Labeling efficiency can be very close to 100% for PASL, but also check control condition

0

50

100

150

200

250

300

0 200 400 600 800 1000 1200 1400 1600

Inversion time (ms)

MR

-sig

nal (

a.u.

)

kl

80

Quantification of PASL

Wednesday, October 23, 2013Perfusion and permeability 80

Similar, but the temporal duration of the labeling needs to be known:1. Measure it via multi timepoint ASL (see later)2. Fix the duration by a saturation pulse TI1 ≈ 800 ms after the spatial selective

labeling pulse (QUIPSS)

150 300 450 600 750 900 1000 No QUIPSS

81Wednesday, October 23, 2013Perfusion and permeability 81

Alternative: scan dynamically the inflow of label

But at the cost of coverage and SNR (flipangle <90°)Arterial spin labeling

28

82

Example of multi timepoint ASL


Courtesy: Esben Petersen and Xavier Golay


Conclusions

• Arterial spin labeling is based on inversion of inflowing blood

• PCASL is the recommended approach

• Quantitative values are in line with gold standard (PET)

• Application areas include tumors, large vessel disease, acute

stroke, dementia, etc

• ASL can also be used for cognition research

• New techniques image the inflow of labeled spins dynamically

and can map flow territories



Acknowledgements

• Leiden University Medical Center• Naj Mahani

• Wouter Teeuwisse• Sophie Schmid• Xingxing Zhang• Serge Rombouts• Jeroen van der Grond

• Amsterdam Medical Center, NL• Sanna Gevers• Dennis Heijtel• Aart Nederveen• Henk-Jan Mustaerts

• University Medical Center Utrecht

• Jeroen Hendrikse

• Reinoud Bokkers

• Esben Petersen

• Kiel University, Germany

• Michael Helle

• UT Southwestern, Dallas, USA

• Hanzhang Lu

• Vanderbildt University, USA

• Manus Donahue

Date post:	27-Mar-2018
Category:	Documents
Upload:	buithuy
View:	219 times
Download:	2 times

ARTERIAL SPIN LABELING (ASL) - Universitetet i · PDF file1 ARTERIAL SPIN LABELING (ASL)...

Documents