Download arterial spin labeling (asl)

ARTERIAL SPIN LABELING (ASL)
Matthias van Osch, Associate Professor
C.J. Gorter Center for high field MRI, Dpt of Radiology
Leiden University Medical Center
The Netherlands
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)
Quantification of ASL
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Microvasculature
Gray matter
Cast of cerebral human
vasculature
White matter
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1
Perfusion
Cerebral blood flow
amount of blood that enters
the microvasculature per
second
ml blood / min / 100 ml tissue
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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)
Arterial spin labeling
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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
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Acute stroke
66-year old woman presenting within 1 hour after symptom
onset
Bokkers, Hernandez, Merino, Mirasol, van Osch, Hendrikse, Warach, Latour: Stroke. 2012 May;43(5):1290-4
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Acute stroke
Perfusion deficits
Significant perf / diff mismatch
DSC (n = 64)
DSC (n = 64)
ASL
Yes
No
ASL
Yes
Yes
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4
Yes
18
6
No
7
21
No
2
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Interrater agreement
Interrater agreement
•
DSC: 0.64
•
DSC: 0.74
•
ASL: 0.6
•
ASL: 0.51
No
Bokkers, Hernandez, Merino, Mirasol, van Osch, Hendrikse, Warach, Latour: Stroke. 2012 May;43(5):1290-4
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Acute stroke
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
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ASL in Alzheimer’s Disease
Alzheimer’s
Axial
Sagittal
Control
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):75-82
Forebrain-dominant deficit in cerebrovascular reactivity in Alzheimer's disease.
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Brain tumor (Glioblastoma multiforme)
ASL
DSC-MRI
Scanned by technicians, post-processing on the console
Visit Philips LUMC
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Vasodilatory capacity (Acetazolamide)
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Vasodilatory capacity
Advantage of perfusion MRI: Reactivity in sub-regions, e.g.
hypertensive SVD versus CAA
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Pharmacological MRI
Visit Philips LUMC
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Superselective ASL:
labeling of single small arteries
2 cm
Tuneable labeling spot with effective labeling thickness of only 1-2 cm
In collaboration with Kiel
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Arterio-venous malformation
ASL angiography
http://www.avmsurgeon.com/aboutavms.html
LIBC
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In collaboration with Kiel
Patient with Arterio-Venous-Malformation
• 48yo ♂ patient, symptomatic AVM (severe headaches)
In collaboration with Kiel
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In collaboration with Kiel
Patient with Arterio-Venous-Malformation
Selective ASL of major brain feeding arteries did not provide the
requested information:
• ICA right
• ICA left
• BA
In collaboration with Kiel
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In collaboration with Kiel
Patient with Arterio-Venous-Malformation
TOF-MIP
AVM
AVM
AVM
Ø = 2.1 mm
Ø = 3.0 mm
T1w
Superselective ASL performed
exclusively on feeding vessels
of the AVM.
ASL pre-surgery
In collaboration with Kiel
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Wednesday, October 23, 2013
In collaboration with Kiel
Patient with Arterio-Venous-Malformation
TOF-MIP
Ø = 1.2 mm
Ø = 2.1 mm
T1w
Superselective ASL performed
on remained vessels (former
feeding vessels of the AVM).
ASL post-surgery
In collaboration with Kiel
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In collaboration with Kiel
Patient with Arterio-Venous-Malformation
T1w
1. Changes of the territorial
distribution of cerebral
perfusion 24h after surgery.
ASL pre-surgery
Decreased steal effect
after removal of AVM.
ASL post-surgery
2. Temporal speech disorders
of the patient after surgery.
fMRI (language)
In collaboration with Kiel
Parts of Wernicke‘s area
supplied by former feeding
vessels of AVM (proved by
fMRI).
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Patient 1
ASL in Meningeoma 3T 02/2011
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Patient 1
ASL in Meningeoma 3T 02/2011
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Patient 1
ASL in
TOF
Meningeoma 3T 06.10.2011
TOF MIP
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Patient 1
T2
ICA ri + le
ICA + Menigia Media left
global
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T1 CE
Patient 1
02/2011
T1 CE
10/2011
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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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Arterial spin labeling (ASL)
Spatial selective inversion
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Arterial spin labeling (ASL)
Spatial selective inversion
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Arterial spin labeling (ASL)
30×
Label
Spatial selective inversion
-
Control
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Arterial spin labeling (ASL)
Continuous Labeling (CASL)
Pseudo continuous (pCASL)
Pulsed Labeling (PASL)
Slab selective inversion pulse
Arterial spin labeling
Adiabatic inversion plane
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Timing differences between PASL and CASL
Arterial spin labeling
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Half-time of tracer
100
90
80
Signal (%)
70
60
50
40
30
16%
20
10
0
0
1
2
3
4
5
6
7
8
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Time (s)
The labeled spins decay with the longitudinal relaxation time T1
(T1,blood≈1650 ms @ 3Tesla)
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Arrival-time of label
•Transport time to imaging slice is
1-3 s
approximately 1 sec
pCASL
•Probably takes another 1-1.5 s to
PASL
reach capillary bed
Arterial spin labeling
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Arrival-time of label vs decay of tracer
100
90
1-3 s
80
70
pCASL
Signal (%)
60
PASL
50
40
30
20
10
0
0
1
2
3
4
5
6
7
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Time (s)
Wait long for arrival of spins in microvasculature
Image as quickly possible due to loss of label
Arterial spin labeling
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Loss of label: longitudinal relaxation
100 ms
300 ms
600 ms
Inflow of label
Angiogram
1000 ms
1500 ms
2100 ms
2600 ms 3000 ms
3500 ms
Decay of label
Perfusion
Noise
The labeled spins decay with the longitudinal relaxation time T1
(T1,blood≈1650 ms @ 3Tesla)
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Problem in patients: delayed arrival
100 ms
300 ms
600 ms
Inflow of label
Angiogram
1000 ms
1500 ms
2100 ms
2600 ms 3000 ms
3500 ms
Decay of label
Perfusion
Noise
The labeled spins decay with the longitudinal relaxation time T1
(T1,blood≈1650 ms @ 3Tesla)
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MIP (merged)
Example of ASL angiography
Delay = 400 ms
MIP (ICA right)
MIP (ICA left)
MIP (TOF)
MIP (BA)
Example of ASL perfusion imaging
Delay =1650 ms
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Magnetization transfer effect
• Macromolecules have 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)
+90°
+90°
acquisition
Label
acquisition
slice selective
inversion
+90°
-90°
acquisition
Control
acquisition
PASL-FAIR (Kim)
180°
acquisition
Label
acquisition
slice selective
inversion
Venous label 180º
acquisition
Control
acquisition
Non-selective
inversion
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Continuous ASL: single slice (Williams)
acquisition
Label
acquisition
Inversion plane
acquisition
Control
acquisition
Inversion plane
Above imaging
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
Grz
RF
1Garcia
Labeling
(1650
pulses)
and
Alsop, ISMRM 2005
Steady-state for a series of RF-pulses
Garcia and Alsop, ISMRM 2005
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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
Gradient
strength
Magnetic field ~
rotating speed of spins
Phase change ∝ Gradient strength * x * ∆t
Pseudo continuous ASL
Gr z
Gradient
Phase
Between 2 RF pulses there is an extra gradient to create flow induced
phase differences that takes the magnetization towards inversion
Pseudo continuous ASL
With a correct
change in phase the
magnetization is
tipped to inversion
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Pseudo continuous ASL
Grz
Label
RF
Grz
Control
RF
Control situation
Grz
Control
RF
(p)CASL or PASL?
(p)CASL
0 sec
?
1 sec
2 sec
3 sec
2 sec
3 sec
4 sec
delay
PASL
0 sec
Arterial spin labeling
delay
1 sec
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(p)CASL or PASL?
delay
(p)CASL
0 sec
1 sec
2 sec
delay
PASL
0 sec
4 sec
Faster
More averages
1 sec
Arterial spin labeling
3 sec
2 sec
3 sec
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(p)CASL or PASL?
1.5-2 sec of label
delay
(p)CASL
0 sec
1 sec
2 sec
3 sec
4 sec
Spatial label, but how long in time?
delay
PASL
0 sec
1 sec
Arterial spin labeling
2 sec
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3 sec
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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)
Arterial spin labeling
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(p)CASL or PASL?
1.5-2 sec of label
delay
(p)CASL
sec
1 sec
SNR ×2 0~500-800ms
declared
+ uncertainty!
“workhorse”
2 sec
3 sec
2 sec
3 sec
4 sec
delay
PASL
0 sec
1 sec
Arterial spin labeling
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Recommendation for labeling approach
pCASL
Quantification
labeling of ASL
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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
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2D Echo Planar Imaging, cartesian
slice 1
slice 2
slice 3
RF
Gslice
Gphase
Gread
Acq.
• Readily available on most scanners
• Single shot
1 slice per excitation, ~ 25 ms per slice
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Gent, 02-04-2010
3D GRASE
RF
Gslice
Gphase
Gread
Acq.
• Enables single shot whole brain imaging
• Relatively high signal to noise
• Blurring in slice encode direction
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Gent, 02-04-2010
Background suppression
• ASL is a subtraction technique
Static tissue
Static tissue
Labeled spins
• Due to movements, and respiratory and cardiac noise the
static tissue can show large signal variations
• Use background suppression to minimize noise
Arterial spin labeling
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Background suppression, principles
3200 ms
Reminder 1
pCASL
Do not affect label
inv
BS
sat
timing
• Saturation is spatially
selective on brain
• Inversion is global
1
GM
GM
WM
GM
WM
CSF
MZ
0.5
0
0
1000
2000
2000
3000
3000
3000
Reminder 2
• BS affects different
tissues equally
4000
4000
4000
-0.5
-1
time
time (msec)
(msec)
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Arterial spin labeling
Background suppression, principles
3200 ms
Reminder 1
pCASL
Do not affect label
inv
BS
sat
timing
• Saturation is spatially
selective on brain
• Inversion is global
1
GM
WM
CSF
MZ
0.5
0
0
1000
2000
3000
Reminder 2
• BS affects different
tissues equally
4000
-0.5
Reminder 3
Equal sign for all tissues
-1
• If not: intra voxel
cancellation
time (msec)
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Arterial spin labeling
Background suppression, principles
3200 ms
pCASL
BS
sat
timing
inv1
inv2
1
GM
GM
WM
GM
WM
CSF
MZ
0.5
0
Reminder 4
BS affects tissues equally
0
1000
2000
2000
3000
3000
3000
-0.5
-1
4000
4000
4000
• To null more tissues,
more inversion pulses
are needed
time
time (msec)
(msec)
Arterial spin labeling
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BS and signal changes
1
GM
WM
CSF
MZ
0.5
0
-0.5
-1
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Arterial spin labeling
Timing in Background Suppression
MZ
0.5
GM
WM
CSF
0
Reminder 5
• 2D imaging gives
decrease of BS in
subsequent slices
• effect on 3D less severe
-0.5
time (msec)
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Arterial spin labeling
Timing in Background Suppression
MZ
0.5
GM
WM
CSF
0
Reminder 5
• 2D imaging gives
decrease of BS in
subsequent slices
• effect on 3D less severe
-0.5
time (msec)
2D-EPI
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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
Perfusion
permeability
Arterial
spinand
labeling
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What is recommended?
Quantification
Quantification
ofofASL
ASL
Arterial
spin labeling
68
White paper recommendation
Quantification
Quantification
ofofASL
ASL
Arterial
spin labeling
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White paper recommendation
Quantification
ofofASL
Quantification
ASL
Arterial
spin labeling
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23 October 2013
White paper recommendation
Quantification
Quantification
ofofASL
ASL
Arterial
spin labeling
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Recommendation
Conversion to ml/100ml/min
∆M (ASL-signal)
ASL is based on inversion
Labeling efficiency
Quantification
Quantification
ofofASL
ASL
Arterial
spin labeling
M0: reference for arbitrary scaling of signal
intensities in MRI: proton density scan corrected
for difference in proton content between water
and tissue
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Recommendation
,
=
,
,
,
,
Quantification
QuantificationofofASL
ASL
,
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Half-time of tracer
100
90
80
Signal (%)
70
60
50
40
30
16%
20
10
0
0
1
2
3
4
5
6
7
8
9
Time (s)
The labeled spins decay with the longitudinal relaxation time T1
(T1,blood≈1650 ms @ 3Tesla)
74
Arterial spin labeling
Recommendation
,
,
=
,
,
,
,
T1-relaxation
PLD
labeling
Quantification
Quantification
ofofASL
ASL
Arterial
spin labeling
imaging
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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)
Quantification of ASL
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kl
Labeling efficiency of PASL
300
MR-signal (a.u.)
250
200
150
100
50
0
0
200
400
600
800
1000
1200
1400
1600
Inversion time (ms)
Remember: switch off pre-saturation pulses and post-labeling saturation
Quantification of ASL
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kl
Labeling efficiency of PASL
300
MR-signal (a.u.)
250
200
150
100
50
0
0
200
400
600
800
1000
1200
1400
1600
Inversion time (ms)
Remember: switch off pre-saturation pulses and post-labeling saturation
Remember: modulus data rectifies noise
Quantification of ASL
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26
kl
Labeling efficiency of PASL
300
MR-signal (a.u.)
250
200
150
100
50
0
0
200
400
600
800
1000
1200
1400
1600
Inversion time (ms)
Labeling efficiency can be very close to 100% for PASL, but also check
control condition
Quantification of ASL
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Quantification of PASL
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
Perfusion and permeability
450
600
750
80
900
1000
No QUIPSS
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Alternative: scan dynamically the inflow of label
Perfusion
permeability
Arterial
spinand
labeling
But at the cost of coverage and SNR (flipangle <90°)
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Example of multi timepoint ASL
Courtesy: Esben Petersen and Xavier Golay
Perfusion
permeability
Arterial
spinand
labeling
82
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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
Perfusion and permeability
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Acknowledgements
• Leiden University Medical Center
•
•
•
•
•
•
• University Medical Center Utrecht
Naj Mahani
Wouter Teeuwisse
Sophie Schmid
Xingxing Zhang
Serge Rombouts
Jeroen van der Grond
• Jeroen Hendrikse
• Reinoud Bokkers
• Esben Petersen
• Kiel University, Germany
• Michael Helle
• Amsterdam Medical Center, NL
•
•
•
•
Sanna Gevers
Dennis Heijtel
Aart Nederveen
Henk-Jan Mustaerts
• UT Southwestern, Dallas, USA
• Hanzhang Lu
• Vanderbildt University, USA
• Manus Donahue
Quantification of ASL
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