Basics of Quantification of ASL

1

Basics of Quantification of ASL

Matthias van Osch

223 September 2013Quantification of ASL 2

Contents

• Thoughts about quantification

• Some quantification models

• Bloch equations

• Buxton model

• Parameters that need to be estimated

• Labeling efficiency

• M0

• Bolus arrival time

• Bolus width

• T1 of arterial blood/tissue

• T2 of label

• Or use phase contrast MRA to calibrate CBF

Quantification of ASL


Two kinds of quantification

• Multiplication factors to scale to absolute perfusion

(ml/100ml/min) that are constant for the whole image

• Factors that differ within the ASL-image and therefore will

change relative perfusion

• Transit time differences

• Labeling efficiency for different arteries

• Etc


2


Do we need absolute quantification?

• For many studies global scaling factors are not essential

• Scaling of ASL-images with respect to whole brain average

• How does disease affect blood flow distribution

• Relative perfusion of tumor compared to normal appearing

GM/WM

• Comparison with contralateral hemisphere

• Correction for regional differences is often more important

• Absolute quantification is essential for “whole brain” diseases,

like large vessel occlusive disease, neurodegenerative

disease, sickle cell disease, etc

• Especially important when comparing patients to controls

(differences in T1, labeling efficiency, or brain perfusion?)


5

Arterial spin labeling

Monday, September 23, 2013LIBC 5

1) Label blood magnetically (inversion)

2) Wait 1-2 seconds for label to arrive in brain tissue

3) Acquire images of the brain


6

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

na

l (%

)

The labeled spins decay with the longitudinal relaxation time T1

(T1,blood≈1650 ms @ 3Tesla)

16%


3

7Monday, September 23, 2013Arterial spin labeling 77

•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


8Monday, September 23, 2013Arterial spin labeling 88

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)

Sig

nal (

%)

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

1-3 s


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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

The labeled spins decay with the longitudinal relaxation time T1

(T1,blood≈1650 ms @ 3Tesla)

Angiogram Perfusion Noise


4

10

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.

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Quantification models I: Bloch


Inflow of label Outflow of label

Under assumption of well mixed compartment

Solution steady state:

Correction for differences in water content


12

Quantification models II: Buxton


Magn Reson Med. 1998 Sep;40(3):383-96


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Formulation of ASL signal as a convolution

Delivery function Normalized arterial

concentration of magnetization at

voxel

Residue functionFraction of tagged spins arrived at t’

and still present at t

Relaxation functionRelaxation between

t’ and t

Labeling efficiency


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Labeling efficiency

23 September 2013Quantification of ASL 14Quantification of ASL


Labeling efficiency of PASL

• Check inversion efficiency 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)


6



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.)




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.)




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.)


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Labeling efficiency of CASL and pCASL


Gradient More difficult to measure, because inversion is achieved by flow-driven (pseudo-)adiabatic inversion

Labeling efficiency therefore frequently determined by means of simulation of Bloch equations

Which you will be doing this afternoon…


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M0


• Measure M0 with PD-weighted sequence in vein• Use reference ROI (WM or CSF)• Use separate M0 scan

M0 is the equilibrium signal (TR=∞, TE=0) in a voxel containing 100% arterial blood

• Is therefore proportional to voxel volume• Take care of scaling between scans on your scanner (M0 vs ASL)


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Separate M0-scan

• PD-weighted sequence with

similar readout as ASL

• Correct for differences in water

content of tissue and blood

(λWM≈0.82; λGM ≈0.98) 1

• Perform voxel-wise correction

(=division)

• Also possible to use control

image (be aware of T1-effects

and should not be combined

with background suppression!)

1 Herscovitch P, Raichle ME. J Cereb Blood Flow Metab. 1985 Mar;5(1):65-9


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Separate M0-scan

• Automatically correction for regional differences in T2(*)

• Assuming that T2(*) of ASL signal equals T2

(*) of PD-signal (tissue dominated)


23May 200723

Errors in single echo ASL when assuming uniform T2*

Mean relative error in S0,s.e. (%)

slice thickness difference

ROI 5 mm 8 mm p-value

frontal sinus 47 * 54 * 0.002

nasal cavity 37 ** 50 ** 0.000

petrous bones 34 34 0.957

grey matter 1 1 1.000

white matter -7 -7 0.862

• Table shows relative error in S0 calculation from single echo approach assuming a uniform T2*=50 msec

as compared to dual echo approach. Errors can amount to more than 50%.

• In areas close to air containing cavities the error is significantly reduced with smaller slice thickness.

• Relative error in grey and white matter at a higher level is not significant.

60

40

20

0

-20

-40

-60

error map


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Separate M0-scan




• Also correction for B1-inhomogeneities and other scaling factors is achieved

(i.e. parallel imaging)


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Correcting B1-inhomogeneities

0

2

4

6

8

10

12

0 20 40 60 80 100

Excitation angle (degrees)

Err

or

(%)

10% higher B1

10% lower B1

Error in CBF as a function of readout flipangle


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ASL @ 7T

0

20

40

60

80

100

120

140

160

B1 map With correction for B1


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ASL @ 7T

0

20

40

60

80

100

120

140

160

B1 map Without correction for B1


10

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Separate M0-scan




• Also correction for B1-inhomogeneities and other scaling factors is achieved

(i.e. parallel imaging)

• Without correcting for voxel-wise differences in lambda, some errors are made

1 Herscovitch P, Raichle ME. J Cereb Blood Flow Metab. 1985 Mar;5(1):65-9


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Choice of TR


TR = 2000 ms TR = 10000 msQuantification of ASL

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M0 in CSF

•Same readout as ASL•Inversion pulse of background suppression•Perform fit

0

50

100

150

200

250

0 500 1000 1500 2000

Inversion time (ms)

MR

-sig

nal

(a.

u.)


11

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M0 in CSF

0

50

100

150

200

250

0 500 1000 1500 2000

Inversion time (ms)

MR

-sig

nal

(a.

u.)

*,2

*,2

*,2

*,2

,0,0,0 87.0 bloodCSFbloodCSF T

TE

T

TE

CSF

T

TE

T

TE

CSF

bloodCSFblood eMeMM


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Comparison of M0-methods

Courtesy: Chen, Wang, Detre, ISMRM 2011, abstract nr 300

pCASL

FAIR

ROI in CSF ROI in WMVoxelwiseM0-map

VoxelwiseM0-map

correction for λWM and λGM

Control image as

estimate for M0


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Delivery function Normalized arterial

concentration of magnetization at

voxel

12

34Perfusion and permeability

• Later arrival• More relaxation of label

PASL

Input function for PASL

Transit delay

• Early arrival• Little relaxation of label

t

Bolus width


35Monday, September 23, 2013Perfusion and permeability 35

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)


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Bolus width (

• Determined by width of

labeling slab

• Or by extent of RF-coil

• Or is set by QUIPSS-time

(temporal cut-off of the

bolus)

• Can be measured by

fitting multi-TI dataTrailing edge

Courtesy: Bokkers et al, AJNR Am J Neuroradiol. 2008 p. 1698-703


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37Monday, September 23, 2013Perfusion and permeability 37

Choice of QUIPSS time (ms, TI =2400 ms)

150 300 450 600 750 900 1000 No quipps



PASL (p)CASL

Input function for PASL and CASL

Transit delayt t

= Labeling duration



PASL (p)CASL


tt

ttt

tt

etc bloodTt

0

0

)( ,1

tt

ttt

tt

etc bloodTt

0

0

)( ,1


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How to determine t?

Multi TI PASL

Average arterial transit map (284 subjects)

Courtesy: Petersen, Mouridsen, Golay. The QUASAR reproducibility study; NeuroImage Volume 49, Pages 104-113



PASL (p)CASL


tt

ttt

tt

etc bloodTt

0

0

)( ,1

tt

ttt

tt

etc bloodTt

0

0

)( ,1


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T1, blood

Frequently, the value is taken from literature experiments in bovine blood

Lu et al, Magn Reson Med. 2004,p 679-82

Silvennoinen,et al, Magn Reson Med. 2003,p 568–571

4.7Tesla 3.0Tesla


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T1, blood


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T1, blood

Varela et al. NMR Biomed. 2011 Jan;24(1):80-8Quantification of ASL

4523 September 2013T1 measurement 45

T1, blood measurements

1350

1600

1850

2100

1.5T 3T 7T

T1

, b

loo

d (

ms

)

Males Females


Zhang, Petersen, Ghariq, De Vis, Webb, Teeuwisse, Hendrikse, van Osch. Magn Reson Med 2012

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label

Tissue Outflow:f·Mv=f·Mb/λ

Assumption of well-mixed compartment

Residue functionFraction of tagged spins arrived at t’

and still present at t

r(t)=exp(-ft/λ)


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23 September 2013Quantification of ASL

Relaxation functionRelaxation between

t’ and tWhich T1? T1 of blood or of tissue?

Where is my label? Does it exchange immediately?


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Exchange of label?

Monitor T2-changes as a function of delay time

GM WM

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Two compartment model

Conclusion: T1,blood is best candidate, especially since moment of exchange is often unknown


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≈ 1 PASL≈ 0.65 CASL≈ 0.82 pCASL

PASL

CASL

exp(-ft/λ) exp(-t/T1,bl)


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Buxton model: putting everything together

-0.1

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0 0.5 1 1.5 2 2.5 3

Transit time

Inflow of label

Decay and outflow of label


18

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Buxton model results

-0.1

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

0 0.5 1 1.5 2 2.5 3

CBF 108; TA=0.7; tau=0.8

CBF 80; TA=0.5; tau=1.2

CBF 88; TA=0.5; tau=0.8

Sin

gle TI


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Influence of width of input function

-0.1

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0 0.5 1 1.5 2 2.5 3

Tau = 0.3 s

Tau = 0.6 s


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Buxton fit to multi-TI data

-0.1

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

0 0.5 1 1.5 2 2.5 3

CBF 108; TA=0.7; tau=0.8

CBF 80; TA=0.5; tau=1.2

CBF 88; TA=0.5; tau=0.8


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Post-processing of (multi-TI) PASL

• QUASAR: deconvolution with

input function

• Voxel-wise or ROI-wise fitting

of Buxton model

• Fixation of parameters

(especially, by means of

QUIPSS)

• See Esben’s presentation of

tomorrow

AIF GM

WM residue

Petersen et al, MRM 55:219–232 (2006)Quantification of ASL

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What is recommended?


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White paper recommendation


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Table 3 of white paper


Parameter Value

λ (blood-brain partition coefficient) 0.9 ml/g (1)

T1, blood at 3.0 Tesla 1650 ms (2)

T1, blood at 1.5 Tesla 1350 ms (3)

α (labeling efficiency) for PCASL 0.85 (4)

α (labeling efficiency) for PASL 0.98 (5)

1) Herscovitch P. JCBFM1985;5(1):65-692) Lu H. Magn Reson Med 2004;52(3):679-6823) Lu H. Magn Reson Med 2003;50(2):263-274.4) Dai W. Magn Reson Med 2008;60(6):1488-14975) Wong E. Magn Reson Med 1998;40(3):348-355

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Recommendation


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

ASL is based on inversion

Labeling efficiencyM0: proton density scan corrected for difference in proton content between water and tissue


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Recommendation


,

, ,

= , , ,


63

Amount of label


,

, ,

= , , ,

labeling imagingPLD

,∙

, ,0

= , 1 ,

T1-decay during delay time


22

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Quantification too difficult? Use PC-MRI!

Measure blood flow in the internal carotid arteries and calibrate

perfusion maps based on a tissue segmentation of a 3D-T1

scan


Aslan, et al. Magn Reson Med. 2010 Mar;63(3):765-71

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Is this all about quantification?

No!! Think about:

• Dispersion of the bolus of labeled spins

• Dependency on cardiac cycle

• Motion artifacts

• Scanner problems (spikes, drift, instabilities)

• Intersubject differences

• Etc, etc, etc

• More research needed!



Acknowledgements

• Leiden University Medical Center

• Wouter Teeuwisse

• Sophie Schmid

• Xingxing Zhang

• Jeroen van der Grond

• Mark van Buchem

• University College London,UK

• Xavier Golay

• Amsterdam Medical Center, NL

• Sanna Gevers

• Aart Nederveen

• University Medical Center Utrecht

• Jeroen Hendrikse

• Reinoud Bokkers

• Esben Petersen

• UT Southwestern, Dallas, USA

• Hanzhang Lu

• Kiel University, Germany

• Michael Helle


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Basics of Quantification of ASL