Download Stroke

Acute stroke imaging
and endovascular therapy
MCGILL NEUROLOGY
ACADEMIC HALF-DAY
W E D N E S D A Y , M A Y 1 8 TH 2 0 1 1
ALEXANDRE POPPE MD CM, FRCPC
HOPITAL NOTRE-DAME, CHUM
Outline
 Introduction
 CT or MRI?
 Parenchyma
 Vessels
 Perfusion
 Some cases
 Endovascular treatment of acute ischaemic stroke
Acute stroke imaging: the goals
 Effectiveness of AIS therapy (e.g. thrombolysis) is
time-dependent and requires rapid, accurate
diagnosis
 Imaging is essential to make a CORRECT diagnosis
 R/O ICH
 R/O stroke mimics (tumours, SDH etc.)
 Clinical features do not reliably differentiate AIS
from ICH
ICH or AIS?
 55 y.o. male with acute left hemiparesis, N/V and
headache
Courtesy K. Butcher
CT or MRI?
bmj.com
aspectsinstroke.com
The ideal brain imaging technique
 Widely available
 Inexpensive
 Not harmful
 Fast
 Easy access to patient
 Differentiate AIS from ICH and mimics
 Provide good anatomical resolution
 Identify irreparably damaged tissue from salvageable
tissue
Adapted from Stroke: practical management. 3rd ed. 2007
Computed tomography (CT)
 Clinical use for almost 40 years
 Axial images by spiral acquisition using x-rays
 0.5 – 1.0 cm (anterior-middle fossa)
 0.25-0.5 cm (posterior fossa)
 Image acquisition in about 10 seconds
 CT angiography (CTA) requires iodinated contrast
 Non-contrast CT (NCCT): radiation equivalent of
about 150 chest x-rays
Magnetic resonance imaging (MRI)
 In clinical use since the early 1980’s
 Limited use in acute stroke until the last 10 years
 No radiation
 Routine MRI stroke protocol should include:
 DWI: cytotoxic edema
 FLAIR and T2: brain pathology (vasogenic, cytotoxic edema)
 GRE: hemoglobin breakdown products (acute and remote
bleeds)
 T1: brain anatomy
Multimodal CT
Advantages
 Widely-available
 Rapidly accessible
 Less expensive
 Short scanning times
 Few contraindications
 Excellent for exclusion of
ICH
 CTA and CTP possible
with iodinated contrast
Disadvantages
 Lower sensitivity for
acute ischemia (esp.
small volume infarcts)
 Radiation exposure
 Contrast allergy and
nephropathy
 Limited anatomical
coverage for CTP
Multimodal MRI
Disadvantages
Advantages
 Excellent sensitivity for
acute ischemia
 Reliable exclusion of
ICH and stroke mimics
 Vessel and perfusion
imaging possible with
gadolinium
Less available
Longer scanning times
More expensive
Physically difficult for
acutely-ill patients (1/3
require intervention
during scan)
 15-20% of acute stroke
patients unable to
undergo MRI




CT vs MRI: acute infarct detection
 MRI (DWI) superior to NCCT for detection of AIS
<12hrs, n=221 (OR 25 95%CI 8-79)1



CT sens 16%, spec 97%
MRI sens 78%, spec 96%
Similar results for subgroup <3 hrs (n=90)
 Interrater reliability better for MRI (kappa 0.84) vs
CT (kappa 0.51)2
 False-negative DWI in


Posterior circulation AIS
Clinically mild stroke (NIHSS <4)
 With GRE, MRI = CT for ICH detection
1.
2.
Chalela et al. Lancet 2007
Fiebach et al. Stroke 2002
CT vs MRI: acute infarct detection
 MRI useful for
 Small subcortical infarcts
 Brainstem infarcts
 Small cortical infarcts (isolated or embolic shower)
 DWI can differentiate acute from chronic lesions
Small subcortical infarcts
Brainstem infarcts
Isolated cortical infarcts
“right cortical hand”
Multiple cortical infarcts
Based on 4 prospective studies:
However...
 CT remains the modality
of choice at most
Canadian stroke centres
The ischemic penumbra1
 Acute arterial occlusion
reduced CBF
 Infarct core:

www.radiologyassistant.nl


CBF too low to sustain
cellular membrane integrity
(ion pump failure)
<10ml/100g/min
Tissue death within minutes
 Ischemic penumbra:
 CBF too low to maintain
electrical activity, but enough
to maintain membrane
integrity (1020ml/100g/min)
 Potentially salvageable tissue
Courtesy
K. Butcher
Kidwell C
1.Astrup Stroke 1981
The ischemic penumbra
 Penumbral tissue:
 hypoperfused, hypoxic but structurally intact
 At risk for infarction if perfusion not restored (timedependent)
 Current acute stroke therapies aim to prevent
conversion of penumbral tissue into infarcted tissue



Restoring perfusion (CBF) by recanalizing AOL
“Buying time” to recanalize AOL by augmenting collateral
circulation
Limiting recruitment of penumbra into core using
“neuroprotection”
Le saint graal...
 Can imaging help us
select those patients who
are the best candidates
for reperfusion therapy?
 And conversely exclude
those with nothing to
gain/at high risk for
hemorrhage?
 Help guide which
therapy to use?
 Help with
prognostication?
What should we image?
 Parenchyma
 NCCT
 MRI (DWI, FLAIR, T2)
 Vessels
 CTA
 MRA
 TCD
 Perfusion (?penumbra)
 CTP
 MRI-PWI
Parenchymal imaging: CT
 Identifies areas of recent infarction as
 Hypoattenuation (reflects increased tissue water)
 Loss of grey-white matter differentiation
 Sulcal effacement/local swelling or mass effect
Subacute infarct
(>24 hours)
Courtesy K. Butcher
Parenchymal imaging: CT
Early ischemic changes (EICs)
 Insular ribbon

ICA terminus occlusion, proximal and distal M1 occlusion
 Lentiform nucleus
 ICA terminus occlusion, proximal M1 occlusion
 Corical ribbon
 Proximal or distal MCA, ACA or PCA occlusion
Stroke territory: MCA 60%, PCA 14%, ACA 5%, VB 5%
Always compare to contralateral “normal” side
Hypoattenuation and sulcal effacement
Courtesy K. Butcher
Hypoattenuation = infarct core (not reversible)
Isolated sulcal effacement/cortical swelling
 Rare (1%)1
 May represent
increased CBV via
compensatory
vasodilation
secondary to
decreased CPP
 May be reversible
(penumbra)
Puetz V et al. Int J Stroke 2009
1. Von Kummer R et al. Radiology 1997
Early ischemic changes
May be accentuated by “narrow” windows (W: 130HU, C: 28-36 HU)1
1. Lev MH. et al Radiology 1999
Early ischemic changes
 NINDS trial did not use EIC as exclusion criterion
 31% of patients have EIC
 No treatment modifying effect of EIC1
 ECASS-1 trial introduced the “1/3 MCA rule”2
 ≥2 regions involved (frontal, parietal, temporal, basal ganglia)
 If <1/3 MCA affected, better prognosis
 But no treatment modifying effect
 Only modest interrater reliability for 1/3 rule3,4
1.
2.
Patel SC et al. JAMA 2001
Von Kummer R et al. Radiology 1997
3. Grotta JC et al. Stroke 1999
4. Wardlaw JM et al. J Neurol Neurosurg Psychiatry 1999
Alberta Stroke Program Early CT Score
ASPECTS
 Systematic approach to identifying EICs in the MCA
territory1
 10 regions of interest are allotted 1 point each
 Weighted volumetric scale (smaller subcortical
structures given equal weight to larger cortical ones)
 1 point removed for each affected area
(hypoattenuation and/or focal swelling)
NORMAL = 10
ASPECTS <5 ≈ >1/3 MCA
1. Barber PA et al. The Lancet, 2000.
ASPECTS
56M with R hemiplegia and global aphasia
ASPECTS?
Caudate, insula, lentform = 7
Courtesy K. Butcher
ASPECTS
 EIC should be present on at least 2 cuts
 Watch for false-positives due to
 Motion artifact
 Head tilt
 Bony artifact (e.g. beam-hardening)
 Volume averaging (e.g. enlarged CSF spaces)
 If in doubt, do not call a region abnormal
 Good inter-observer reliability (kappa 0.71-0.81 for
dichotomized ASPECTS >7 and ≤7)
 Reliable in “real time”, improves with experience1
1. Coutts SB et al. Stroke 2004
ASPECTS and Prognosis
 Linear relationship with
favourable functional
outcome (esp. ASPECTS
6-10)
 For every point decrease,
OR 0.81 (95% CI 0.75–
0.87) for favourable
outcome
 ASPECTS 6-10: 50%
good outcome
 ASPECTS 0-3: 15% good
outcome
Hill MD et al. CMAJ 2005
ASPECTS and ICH risk
 Very low ASPECTS may be associated with increased
risk of sICH in NINDS1


ASPECTS 0-2: 20%
ASPECTS 3-10: 4.5-5%
1. Demchuk AM et al. Stroke 2005
ASPECTS and Response to tPA
 Lower ASPECTS associated with worse outcome
regardless of tPA
 No evidence that ASPECTS modifies effectiveness of
IV-tPA given between 0-3hrs
 No evidence to withhold tPA within 0-3hrs based on
ASPECTS alone
 Beyond 3 hrs, poor ASPECTS may argue against
pursuing IA therapy
1. Demchuk AM et al. Stroke 2005
ASPECTS and Treatment decisions
< 4.5 hours
 IV-tpa should not be withheld based on ASPECTS
 Low ASPECTS is associated with worse outcome,
possible higher ICH risk
 Low ASPECTS should prompt re-evaluation of onset
time
 ASPECTS <5 might dissuade IA approaches
Puetz V et al. Int J Stroke 2009
ASPECTS and Treatment decisions
>6 hours
 “Wake-up” strokes
 Good scan – occlusion paradigm

High ASPECTS (esp. with documented proximal AOL) might
support acute treatment (IV or IV-IA)
Puetz V et al. Int J Stroke 2009
Posterior circulation ASPECTS
 For basilar occlusion (10 regions, normal = 10)
 Uses NCCT or CTA-SI
 In a small cohort, score >7 predicted favourable
outcome (RR 12.1; 95% CI 1.7–84.9)1
1. Puetz V et al. Stroke 2008
ASPECTS and other modalities
 ASPECTS has also been applied to
 MRI-DWI (ASPECTS ≤ 5 predicts poor functional outcome)1
 MRI-PWI
 CTP
 CTA-SI
1. Kimura K et al. Stroke 2008
Hemorrhagic transformation
 Hemorrhagic infarction 1 (HI1)
 small petechiae along the margins of the infarct
 Hemorrhagic infarction 2 (HI2)
 confluent petechiae within the infarcted area but no spaceoccupying effect
 Parenchymal hematoma 1 (PH1)
 blood clots in 30% of the infarcted area with some slight spaceoccupying effect
 Parenchymal hematoma 2 (PH2)
 blood clots in >30% of the infarcted area with a substantial
space-occupying effect
Larrue V et al. Stroke 2001
Vascular imaging
 Stroke is a vascular disease (brain is the innocent
victim of vascular pathology)
 Imaging vessels is key to understanding the
causative occlusion and the stroke mechanism
 Presence of intracranial AOL predicted by


NIHSS (80% of NIHSS ≥10)
ASPECTS (100% of ASPECTS ≤5 within 6 hrs)1
1. Barber PA et al. J Neurol Neurosurg Psychiatry 2004
Seeing thrombus on non-vascular imaging
 Hyperdense vessels


Thrombus
False-positives: calcification, polycythemia
 Hyperdense MCA (HMCA)1



M1 thrombus
Incidence 5% of unselected stroke, up to 50% of MCA stroke
High specificity, low sensitivity for thrombus
 MCA dot sign2



M2 or M3 branch thrombus
16% incidence among unselected acute stroke patients
Associated with better outcome than HMCA
1. Tomsick TA et al. Neuroradiology 1989
2. Barber PA et al. Stroke 2001
Hyperdense MCA sign (HMCA)
Courtesy K. Butcher
MCA dot sign
Courtesy K. Butcher
 23F RHD
 Decreased LOC, N/V
 Dysconjugate gaze
 Tetraparesis progressing
over hours
 23F RHD
 L hemiparesis
 Dysarthria
 L hemispatial neglect
 NIHSS 15
Vascular imaging
CT-Angiography
 Circle of Willis only or
aortic arch-to-vertex
 Aortic arch, great vessels
of the neck, intracranial
arteries up to distal
secondary or tertiary
branches
 Contrast: 90-120 cc
 Radiation: 8mSV (= CT
chest or CT abdomen)
 Time: about 10 minutes
CTA concerns
 Contrast allergy – rare (0.1%)1
 Contrast nephropathy - rare2
 2% (2/93) in patients without baseline creatinine
 No cases requiring dialysis
1. Hunt CH et al. Am J Roentgenol 2009
2. Krol AL et al. Stroke 2007
CTA and Diagnosis
 Identifies culprit AOL if in proximal intracranial
artery or branches (95% accuracy)
 Identifies possible stroke mechanism






Extracranial large-artery atherosclerosis (stenosis, ulceration,
floating thrombus)
Arterial dissection
Intracranial vasculopathy (atherosclerosis, RCVS, vasculitis)
FMD, aneurysms
Aortic arch atherosclerosis (size, ulceration, thrombus,
pedunculation)
Pulmonary embolism (apical lung cuts)
Vascular imaging and Prognosis
 Favourable prognosis and survival are highly
correlated with recanalization and time to
recanalization1
 Recanalization rates are influenced by




Thrombus location (10% distal ICA, 15-20% M1, ≥30% M2M3)
Thrombus size (clot burden)
Residual flow through/around thrombus
Presence of robust collaterals
 No conclusive evidence that CTA provides prognostic
information beyond NIHSS
1. Rha JH et al. Stroke 2007
Clot burden score
 10 point score (normal =
10)
 CBS <7 associated with
low rate of recanalization
with IV-tPA
Puetz V et al. Int J Stroke 2008
Vascular imaging and Treatment decisions
 “Good scan - occlusion” paradigm

Consider treating beyond 4.5 hours
 Absence of proximal thrombus

IV-tPA alone
 Distal thrombus or intracranial non-occlusive thrombus
(iNOT)1

IV-tPA alone
 Mild-moderate deficit (NIHSS <10) but thrombus visible


High-risk of early deterioration
May favour reperfusion therapy
 High-grade ipsilateral carotid stenosis

Urgent CEA or CAS
1. Puetz V et al. Stroke 2009
Vascular imaging and Perfusion
CTA source images (CTA-SI)
 “Hypocontrastation”
correlates with infarct core
 Sensitivity for core
comparable to DWI
 Collateral flow (?penumbra)
 Window W:80 C:40
 May better predict prognosis
than NIHSS
Coutts SB et al. Stroke 2004
Kohrmann M et al. Cerebrovasc Dis 2007
Perfusion imaging
 Goal is to measure perfusion at the tissue level
(microcirculation)
 May provide information about



Infarct core (irreversible injury)
Penumbra (hypoperfused but potentially salvageable tissue)
Benign oligemia (hypoperfused but destined to survive)
 Performed with CT (CTP) or MRI (PWI)
 Generally qualitative (colour-coded maps)
CTP
 Requires special software and post-processing (delay





in generating images)
30-50 cc iodinated contrast
Most scanners only provide 4-8cm of coverage
After contrast bolus, sequential CT slices obtained
As contrast travels through macr0- and
microcirculation, image density changes (HU) over
time
Tissue –Time density curves are generated for each
voxel
CTP
 Maps are derived from the tissue-time density curve
 CBV
 CBF
 TTP
 MTT
 Tmax
 In acute stroke with AOL
 CBV is decreased (represents infarct core like DWI)
 CBF is decreased
(represent tissue at risk)
 TTP, MTT and Tmax are increased
CTP
CTP: Mismatch hypothesis
 CBV or NCCT defines infarct core
 CBF, MTT, TTP or Tmax are tissue at risk
 Penumbra is area where
 CBV is normal
 CBF is decreased
 MTT, TTP and Tmax are prolonged
 If CBV volume < CBF or MTT volume = mismatch
 If CBV volume = CBF and MTT = no mismatch
Prolonged
Penumbra
MTT
Low
Core
CBV
CTP
 Mismatch determined by visual inspection
 If volume difference >20% = mismatch
 Presence of mismatch may suggest salvageable tissue
and possible treatment options beyond 4.5 hours
 If no mismatch, than perhaps no salvageable tissue
and treatment futile
Mismatch
Courtesy K. Butcher
Mismatch
No mismatch
Courtesy K. Butcher
Perfusion imaging
Promise
 Better target patients who stand to benefit
 Avoid treating patients who would not benefit and might be
harmed
 Prolong therapeutic window (tissue window as opposed to
chronological window)
Limitations
 Time delays
 Labour intensive
 Many assumptions (normal contralateral flow, single occlusion)
 Non-standard definitions of maps between centres
 Subjective mismatch determination
Perfusion imaging
Trials testing the mismatch hypothesis in AIS
treatment:
 DIAS, DIAS-2, DEDAS
 EPITHET
Cas 1
ID: Homme 48 ans, droitier
HMA:
 Paralysie gauche et trouble
de la parole soudaine
ATCD:
 Lymphome nonhodgkinien sous ChimioTx
 Consommation de cocaine
IN
 Tabagisme
E/P: SVS
 Hemiparesie G
 Hemianesthesie G avec
heminegligence G
 Dysarthrie
NIHSS 15
Labos: OK
ECG: RSN
CT 1.5 hres post-AVC
1.5 hres
post-AVC
Jour 1 post tPA IV-IA avec Tx endovasculaire
N.B. complications emboliques
Cas 2
ID: Homme 62 ans,
droitier
HMA:
 Faiblesse hemicorps
droit et trouble de la
parole soudaine
ATCD:
 HTA
 Tabagisme
E/P: SVS
 Hemiparesie B-F D
 Aphasie mixte moderee
NIHSS 10
Labos: OK
ECG: RSN
2 hrs post-AVC
Baseline
tPA IV 2.5 hres
post-AVC
Jour 1
Cas 3
ID: Femme 68 ans,
droitiere
HMA:
 Plegie hemicorps D avec
mutisme
ATCD:
 Anemie severe
(rectorragie)
 Tabagisme
E/P: SVS
 Hemiplegie B-F D
 Aphasie globale severe
NIHSS 18
Labos: Hb 60
ECG: FA
Echec de Tx endovasculaire –
angioplastie, MERCI, tPA-IA
Jour 1
Conclusions
 Imaging is essential in acute stroke management
 MRI is superior to CT for detection of acute infarct
 ...CT is more convenient in our setting
 ASPECTS is a useful tool to assess EIC in MCA
strokes and informs prognosis and treatment
 CTA provides diagnostic, etiologic and prognostic
information in AIS
 Perfusion imaging is promising for better patient
selection and longer treatment windows
Game-changer?
Toshiba Aquilion Premium
320 slice
Cine-CTA and whole brain CTP with single contrast bolus
tPA IV




Avantages
Disponibilite
Acces rapide
Facilite d’administration
Benefice clinique
documente dans
plusieurs etudes et
registres
1
Inconvenients
 Faible taux de
recanalisation (TIMI 23)1


CI 10%
ACM proximal 25%
 Hemorragie
intracerebrale
 Hemorragie systemique
Wolpert AJNR 1993, Yamaguchi Cerebrovasc Dis 1993, Mori, Neurology 1992
Approche IA (tPA +/- mecanique)
Avantages
 Meilleurs taux de
recanalisation:




PROACT II 66% ACM
MultiMERCI 57-70%
Penumbra 82%
Stent 75-100%
 Visualisation en temps
reel de la recanalisation
Inconvenients
 Delai entre AVC et angio


PROACT II: 5.3 hrs
IMS-I: 3.5 hrs
 Besoin importants de
ressources (humaines et
materielles)
 Centres specialises
seulement
 Anesthesie/intubation?
IV-IA “bridging”: l’evidence
Emergency Management of Stroke (EMS)
 Stroke 1999
 tPA IV/IA (n=17) versus placebo IV/tPA IA (n=18)
 Meilleure recanalisation (TIMI 2-3) pour IV/IA (81%
versus 50%)
 Pour occlusions M1-M2: 100% recanalisation
IV-IA “bridging”: l’evidence
IMS I
 Jan-Oct 2001
 Open-label, single-
arm pilot study of
IV-IA within 3 hours
in stroke with
NIHSSS ≥ 10
(median 18)
 n=80
 Pour NIHSSS ≥ 20

mRS 0-2 a 3 mois:
IMS I 42%
 NINDS tPA 21%

Comparaison avec cohort NINDS
IV-IA “bridging”: l’evidence
IMS II
 Prolongation de IMS I avec ajout du systeme EKOS
MicroLysus
 n=73
 NIHSSS median = 19
 IMS II versus NINDS tPA

mRS 0-2 a 3 mois: 48% versus 36%
IV-IA “bridging”: l’evidence
RECANALISE
(Mazighi et al. Lancet Neurol
2009)
 Registre prospectif
“before and after”
 tPA IV versus tPA
IV + endovasculaire
IV
(n=107)
IV-IA
(n=53)
P value
Recanalisation
52%
87%
<0.0001
Early
neurological
improvement
39%
60%
0.07
mRS 0-2 at 90
days
44%
57%
0.13
Death at 90
days
17%
17%
0.98
sICH
11%
9%
0.73
Embolectomy devices
MERCI
Embolectomy devices
PENUMBRA
Embolectomy devices
SOLITAIRE
Thrombolyse pour AVC au CHUM
2002-2008
 Taux de thrombolyse: 11.8%
(9% IV, 2.8% IA)
 Onset to treatment time (OTTT):
≤ 2 heures
9.8%
≤ 3 heures
84%
> 3 heures
15.9%
Merci a Dr Lebrun pour ces donnees
IV-IA au CHUM
Annee
Nombre
de cas IVIA
Nombre
de cas IV
Nombre
de cas IA
2003
0
31
3
2004
1
24
7
2005
0
31
9
2006
2
32
9
2007
3
34
7
2008
5
36
11
2009
13
48
10
2010
17
43
12
2011
13
21
4
Merci a R. Cournoyer pour ces donnees
Justifications pour une etude IV vs IV-IA
 Limitations du tPA-IV
 Avantages du IA
 Superiorite potentielle du IV-IA versus IV (EMS,
IMS I et II, RECANALISE)
 Enthousiasme croissant pour l’approche IV-IA
malgre l’absence d’essais cliniques comparant
directment IV-IA et IV
 Superiorite d’une approche endovasculaire dans les
SCA
IMS III
INTERVENTIONAL MANAGEMENT OF STROKE TRIAL
CLINICAL PROTOCOL
A phase III, randomized, multi-center, open label, 900 subject
clinical trial that will examine whether a combined intravenous
(IV) and intra-arterial (IA) approach to recanalization is superior to
standard IV rt-PA (Activase®/Actilyse®) alone when initiated
within three hours of acute ischemic stroke onset.
IMS III
INTERVENTIONAL MANAGEMENT OF STROKE TRIAL
CLINICAL PROTOCOL
The trial is designed to test the hypothesis that there is an overall
absolute difference of 10% in the likelihood of a favorable
outcome for subjects treated with the combined IV/IA approach
overall as compared to those treated with standard IV rt-PA.
Subjects will be randomized in a 2:1 ratio with more subjects
assigned to the combined IV/IA group.
Target enrollment n=900 patients
Good references
Menon BK, Goyal M. Endovascular therapy in acute ischemic
stroke: where we are, the challenges we face and what the
future holds. Expert Rev Cardiovasc Ther. 2011
Apr;9(4):473-84.
Tomsick TA, Khatri P, Jovin T, Demaerschalk B, Malisch T,
Demchuk A, Hill MD, Jauch E, Spilker J, Broderick JP; IMS
III Executive Committee. Equipoise among recanalization
strategies. Neurology. 2010 Mar 30;74(13):1069-76.
Thank you