Arterial spin labeling perfusion:
Basic principles and clinical applications
in neuroimaging
Joana Ramalho, MD
Centro Hospitalar de Lisboa Central, Lisbon, Portugal
University of North Carolina, Chapel Hill, USA
Arterial spin labeling (ASL)
 A technique that uses magnetically labeled
arterial blood water protons as endogenous
tracer.
 Non-ionizing & non-invasive technique useful in:
 All pts (pediatric), pts with renal insufficiency,
repeated follow-ups.
 Quantitative method - blood flow
 Global hypo- or hyper-perfusion states; comparison
between multiple measurements in longitudinal
studies.
Basic principles
 Arterial blood water is labeled by a
RF pulse that inverts or saturates
the longitudinal component of the
MR signal of the protons in the
flowing blood.
Imaging Slab
RF pulse
 After a delay time between
labeling and image acquisition,
labeled spins reach capillaries and
pass into brain tissue, where they
alter the local tissue´s longitudinal
magnetization.
Labeling Plane
Basic principles
 A “flow labeled image or tag image” and a “control
image” are acquired. Static tissue signal is identical in
both, but magnetization of inflowing blood is different;
this difference is: perfusion signal.
Arterial spin labeling
Tag
Control
Tag
Control
Tag
Control
 Multiple labeled–control image pairs are acquired in a
temporally interleaved fashion and averaged to generate
cerebral blood flow (CBF) maps.
 Absolute quantitative perfusion maps are obtained using
the General Kinetic Model Buxton et al.
Artifacts
Susceptibility Artifacts due to:
 Use EPI for rapid image acquisition.
 Presence of blood, surgical materials, and airbone interfaces at the skull base (aerated
paranasal sinuses).
Right putaminal hemorrhage (large arrow), seen as bright signal intensity lesion on
T1W (A), dark signal intensity on SWI (B), and dark signal on ASL CBF map (C).
Metallic object in right occipital region (arrowhead) is seen as high intensity focus on CT
(A), dark on T1W MRI (B), and causing image distortion (arrow) on ASL CBF maps (C).
Artifacts
Motion Artifacts:
 ASL is a subtraction technique, thus it is sensitive
to subject movement.
 Motion is most common artifact in clinical
setting, particularly in hospitalized patients.
A peripheral ring (arrows) of high signal is a common finding in ASL degraded by motion.
Age-dependent ASL variability
 CBF is of low level in peri-natal period, increases to a peak
at 3- 8 years of age, then gradually decreases to adult levels.
A
B
Normal ASL CBF maps in a pediatric patient (A) and an adult patient (B).
Regional hyperperfusion
 Occipital hyperperfusion has been described,
corresponding to visual cortex activation.
Cerebrovascular diseases
A
C
B
Acute cerebral infarction in left MCA territory seen as two foci of low signal intensity on ADC
map (A). MRA (B) demonstrates left ICA occlusion and right MCA stenosis. ASL CBF maps (C)
reveal large area of perfusion diffusion mismatch in left cerebral hemisphere and
hypoperfusion in right MCA territory. Note the high intravascular signal (arrow) in left ICA.
Cerebrovascular diseases
 Delayed arterial transit effects
 Serpiginous high signal in cortex that may represent:
 Labeled arterial blood in feeding arteries at time of image
acquisition
 Collateral circulation through leptomeningeal vessels
resulting in prolonged transit time
 This pattern may have a protective effect and predict
positive clinical outcomes.
Cerebrovascular diseases
A
C
B
Delayed arterial transit effects are also seen over the right hypoperfused area (arrowhead).
Post gadolinium T1W (A) demonstrates left cavernous sinus meningioma (arrow) encasing
left ICA. MRA (B) shows mark narrowed cavernous left ICA (arrow). ASL CBF map (C) shows
delayed arterial transit effects (arrow) in left MCA territory.
“Borderzone sign”
 Zaharchuk et al.: ASL reveals additional abnormalities in
patients with normal dynamic susceptibility contrast
(DSC) MR perfusion studies.
 Low signal in arterial watershed regions with presence of
delayed arterial transit effects on surrounding cortical areas is
termed: “borderzone sign”
 They believe this finding represents labeled blood
remaining in feeding arteries caused by longer-thannormal arrival times, reduced CBF, or a combination of
these.
A
B
C
A 77 year-old female with cognitive impairment. ASL CBF maps (A) shows borderzone sign,
seen as low signal intensity in arterial watershed regions with serpiginous high signal
intensity in the surrounding cortex. FLAIR images (B) reveals nonspecific high signal
intensity in periventricular white matter. MRA (C) is unremarkable.
CNS tumors
A
B
C
Glioblastoma multiforme. Axial postgadolinuim T1 (A) shows avid enhancement of a high
grade neoplasm centered in the thalamic region. The lesion shows high perfusion on
rCBF DSC and ASL CBF maps (A and B).
A
B
C
D
Hipoperfused glioma on ASL. Coronal FLAIR (A) and axial T2 (B) demonstrate a high signal
intensity mass in the left thalamus. Minimal enhancement is seen after gadolinium
administration (C), with corresponding low perfusion on the CBF map.
AJNR 2008; 29:1428-35
A
C
B
Post surgical recurrent glioblastoma multiforme. Axial T2 WI (A), axial postgadolinium T1 WI
(B) and ASL CBF map (C) show an heterogeneous lesion with moderate enhancement and
increase perfusion representing recurrent high grade lesion.
Right cerebellopontine angle meningioma, seen as well circumscribed extra-axial slightly
high signal intensity mass (arrow) on T2WI (A), intense homogeneous enhancement on
post gadolinium T1WI (B), and markedly increased perfusion on ASL CBF map (C).
Non-small cell lung cancer with left frontal metastases. The lesion shows low-to-isosignal
intensity on T2WI (large arrow) (A), ring enhancement on post gadolinium T1WI (B) and
hyperperfusion on ASL CBF map (C) The area of perilesional edema (small arrow) shows
hypoperfusion on ASL CBF map.
Arterio-venous malformation
Right temporal AVM. ASL CBF maps (A) demonstrate bright signal intensity lesion (large
arrow) with linear bright signal intensity adjacent to the right sphenoid ridge (small arrow)
and superficial to the right frontal lobe representing shunting and cortical venous drainage.
Slightly decreased perfusion in right MCA territory is noted, probably reflecting steal
phenomenon. Findings correspond with right ICA DSA (B and C) showing rapid filling of AVM
and drainage into cortical vein over right frontal and temporal lobes.
CNS infections: Cerebral Abscess
D
Abscess in left temporal lobe. T2W (A) shows internal high signal intensity with
peripheral dark signal intensity (arrow). ADC map (B) shows low signal intensity (arrow)
of the abscess content, representing restricted fluid diffusion. Smooth rim enhancement
is noted on post gadolinium T1W (C). ASL CBF map (D) shows hypoperfusion.
Conclusions
 Recent technical and post processing advances
make ASL available for routine clinical practice.
 Several investigations demonstrated that ASL
perfusion is comparable with other more
invasive methods such as DSC MR perfusion
and nuclear medicine techniques.
References
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Liu TT, Brown GG. Measurement of cerebral perfusion with arterial spin labeling: Part
1. Methods. J Int Neuropsychol Soc. 2007; 13:517-525
Brown GG, Clark C, Liu TT. Measurement of cerebral perfusion with arterial spin
labeling: Part 2. Applications. J Int Neuropsychol Soc. 2007; 13:526-538
Deibler AR, Pollock JM, Kraft RA, Tan H, Burdette JH, Maldjian JA. Arterial spin-labeling
in routine clinical practice, part 1: technique and artifacts. AJNR Am J Neuroradiol 2008
29:1228-1234
Deibler AR, Pollock JM, Kraft RA, Tan H, Burdette JH, Maldjian JA. Arterial spin-labeling
in routine clinical practice, part 2: hypoperfusion patterns. AJNR Am J Neuroradiol.
2008;29:1235-1241
Deibler AR, Pollock JM, Kraft RA, Tan H, Burdette JH, Maldjian JA. Arterial spin-labeling
in routine clinical practice, part 3: hyperperfusion patterns. AJNR Am J Neuroradiol
29:1428 –1435
Wolf RL, Detre JA. Clinical neuroimaging using arterial spin-labeled perfusion magnetic
resonance imaging. Neurotherapeutics. 2007;4:346-359
Pollock JM, Tan H, Kraft RA, Whitlow CT, Burdette JH, Maldjian JA. Arterial spin-labeled
MR per fusion imaging: clinical applications. Magn Reson Imaging Clin N Am. 2009;
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Petersen ET, Zimine I, Ho YC, Golay X. Non-invasive measurement of perfusion: a
critical review of arterial spin labelling techniques.Br J Radiol.2006; 79:688-701
Detre JA, Wang J, Wang Z, Rao H. Arterial spin-labeled perfusion MRI in basic and
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Detre JA, Wang J. Technical aspects and utility of fMRI using BOLD and ASL. Clinical
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ASL perfusion quantification
 Arterial transit time - time it takes blood to travel from
tagging region to imaging slices.
 The delay should be chosen according to subject’s condition
 In healthy volunteers a delay of 1 second is suitable
 In pts with cerebrovascular diseases longer delays are needed
 Residual labeled blood in large vessels - may give artificially
high perfusion values in CBF quantification.
Remaining labeled blood in the large vessels.
Different ASL techniques
Continuous
CASL
Pulsed
PASL
Pseudo-continuous
PCASL
Velocity-selective
VS-ASL
Long and continuous RF pulses (2-4
seconds) in combination with a
slice-selective gradient to induce a
flow-driven adiabatic inversion of
the arterial magnetization in a
narrow plane of spins.
Higher SNR > PASL
Short RF pulses (5-20 msec) to
saturate/invert a thick slab (10-15
cm) of blood volume (“tagging
region”).
Higher tagging
efficiency
Intermediate means to take
advantage of CASL’s high SNR and
PASL’s higher tagging efficiency.
Higher SAR
Limited clinical
availability
Arterial spins are labeled based
purely on flow velocity, therefore
eliminating the effect of the transit
delay time.
Lower SNR
MT effects
Higher SAR
Hardware required
Lower SNR
Developmental venous anomaly
A
B
Left frontoparietal DVA on ASL CBF and rCBF DSC maps (A and B). DVA and their
surrounding brain parenchyma demonstrate hyperperfusion. DVA seen as enhancing
dilated medullary veins (arrows) on axial (C) post gadolinium T1W.
Crossed cerebellar diaschisis
Crossed cerebellar diaschisis, or reduced perfusion and atrophy in the cerebellum
contralateral to acute cerebral infarction
Posterior reversible encephalopathy
A
B
C
D
PRES seen as high signal intensity in parasagittal subcortical white matter (arrowheads)
in both parietal lobes on FLAIR images (A and B). ASL CBF maps (C and D) demonstrate
decreased perfusion in affected areas.
33 year-old-female with PRES. DWI (A) and ADC (B) map show restricted fluid
diffusion in bilateral occipital lobes (arrows). ASL map (C) shows increased
perfusion in affected regions (arrow).
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Right glomus jugulare tumor (arrow) is of low signal intensity on T1W (A), heterogeneous
iso- to high signal on T2W (B), enhances homogeneously on post Gd T1W, (C) and has
markedly increased perfusion on ASL CBF map (D).
Epilepsy: Tuberous Sclerosis
Patient with tuberous sclerosis with seizures after temporal cortical tuber ressection.
Post surgical changes of right parietal lobe, with increased perfusion in the posterior
aspect of the surgical bed. Note other high perfusion left parietal lesion, probably
related with a cortical tuber.
Emerging techniques
 Territorial ASL allows labeling and visualization of
perfusion in territories of individual arteries, labeling
only blood flowing through an artery or arteries of
interest.
 ASL at multiple inversion times avoids effect of arterial
transit time. Long scan time often rendering it
impractical especially in sick patients.
 ASL perfusion can also be used as fMRI contrast to
localize task activation as BOLD contrast or as a measure
of brain function independent of specific sensorimotor
or cognitive tasks.