1. Stroke – past
CT Angiography and
CT Perfusion in the
Management of Acute
Stroke
Stroke – present Stroke – present
good outcome with IV tPA(mRS 0-1): 39% vs. 26% 1 IV tPA exclusions / contraindications
most patients arrive too late (>3 hrs for NINDS) 1. > 3 hrs from stroke onset
2. 80 > age > 18
currently, only 0.6-1.8% of strokes get IV tPA 2,3
0.6- 3. pregnancy (up to 10 days postpartum)
4. “symptoms suggestive of SAH” – despite negative CT
5. “rapidly improving or minor symptoms”
6. “seizure at onset of stroke”
7. ever: → history of intracranial hemorrhage
8. within 3 mo: → stroke, serious head trauma, intracranial surgery
Odds Ratio for Favorable Outcome 9. within 21d: → GI/urinary/pulmonary hemorrhage
10. within 14d: → major surgery
11. within 7d: → arterial puncture at a non-compressible site
12. SBP > 185 mmHg or DBP > 110 mmHg
13. aggressive treatment required to reduce BP to specified limits
14. current use of anticoagulants (or recent, with PT > 15s)
15. use of heparin within 48hrs and elevated PTT
16. platelets < 100,000
17. glucose < 50 or > 400 mg per deciliter
18. brain tumour, abscess, aneurysm, AVM
19. bacterial endocarditis
20. known bleeding diathesis – includes renal, hepatic insufficiency
21. etc…
NINDS NEJM 19951,
Katzan JAMA 20002,
Qureshi NRS 20053
Stroke – present “Time is brain”
typical supratentorial large vessel stroke: ~54ml brain is
IV tPA is less effective for severe strokes 1
lost over ~10 hrs
NIHSS ≥ 10: 75% decreased chance of good outcome
NIHSS > 20: only 8% will attain NIHSS=1 after IV tPA
per hour: 830 billion synapses, 120 million neurons, 447
miles of myelinated fibre lost
IV tPA is less effective for large vessel occlusions 2,3
ICA recanalization rate is 1/3 that of MCA each hour, brain effectively ages 3.6 years
hour,
tandem ICA/MCA has poor recanalization & bad prognosis
IV tPA is relatively slow-acting 4,5
slow-
Saver, Stroke 2006; 37:263
TCD over 6hrs → 30% recan (of which ¾ are within 1hr tpa)
tpa)
angio 1hr after tPA → 1/10 ICA/proximal MCA, 1/3 distal MCA
1: NINDS Stroke 1997; 28:2119–2125
2: LInfante Stroke 2002; 33:2066-2071
33:2066-
3: Rubiera Stroke 2006; 37:2301-2305
37:2301-
4: Christou Stroke 2000; 31:1812-1816
31:1812-
5: Lee Stroke 2007; 38:192-3
1

2. Stroke – future? now. Stroke – new tools
Thrombolytics: → Alteplase, Retavase
Treatment of Acute MI
GIIb/IIIa inhibitors: → Reopro, Integrilin
1993
1987 2003
2000
Mechanical disruption: → microwire / snare
PTCA
IV tPA Cypher
Stent
Clot retrieval: → MERCI, Penumbra
Treatment of Acute Stroke Ultrasound Catheter: → EKOS
Angioplasty / Stenting
today → Gateway / Wingspan
1996 2004 ???
1999
IV tPA PROACT II MERCI Retriever
Multimodal
Revascularization
CT: early left caudate head, basal ganglia infarct
Case example:
45 yo male
acute LMCA stroke
R paretic, R hemianopic, R facial droop, dysphasic, dysarthric.
NIHSS = 15
CTP:
Flow
↑↑MTT, ↓CBF, ↑CBV
Interpretation:
small caudate and
frontopolar infarcts,
surrounded by large Volume
(but salvageable)
ischemic penumbra…
Transit Time
2

3. CTA: LM1 occlusion (w/distal collateral) CTA: LCCA/inominate stenosis
AP: Sag:
LCCA origin severe stenosis, 5F sim2 finally pops in but is occlusive (static dye column) T-occlusion equivalent: proximal LA1, LM1 occluded, poor collateralization
All-star 0.014 wire maintains access to LCCA, pigtail arch run shows severe origin stenosis Cross LM1 occlusion with MERIC 18L microcatheter over transend
AP Lateral
1. Aviator 6x30mm over
All-star wire, LCCA
origin angioplastied
2. Sim2 back over All-
star wire into distal
LECA
3. All-star wire then
exchanged for 0.035
stiff exchange
glidewire
4. Sim2 swapped out for
7F concentric balloon
guide over stiff
exchange wire, parked
in LCCA
5. Concentric guide
catheter taken to distal
cervical LICA
6. LMCA occlusion
crossed with 18L
Concentric
microcatheter over
Transend microwire…
3

4. Deploy MERCI L5 retriever Clot retreived, flow restored
AP Lateral AP Lateral
Pre
AP AP Lateral
Post
Post – Arch MRA: LCCA stenosis better, inominate as before, will need tx later
IA Thrombolysis: New Tools
Thrombolytics: Alteplase, Retavase
GIIb/IIIa inhibitors: Reopro, Integrilin
Reopro,
Mechanical disruption: microwire/snare
Clot retrieval: MERCI (X6, L5, variants)
Ultrasound assisted Catheter: EKOS
Balloon Angioplasty
Primary Stenting
4

5. Imaging for stroke intervention
New-generation CTA/CTP = anatomy+physiology
GOAL:
1. faster: <5 min total acquisition time
To select out
2. less motion artifact
patients with viable 3. less dye (CTA+CTP <120ml) → <50ml with 320-slice!
brain tissue at risk 4. CTA (arch to vertex) :
that can be treated • lesion presence/absence/location
with the optimal • lesion accessibility
• a priori knowledge = no guessing!
tool for
5. CTP:
revascularisation
• absolute numbers for CBF, CBV
• 4-8 slices, + post-fossa coverage → full coverage with 320-slice!
HOW? • CBF ≈ penumbra+core; CBV ≈ collateral supply
• CBF/CBV mismatch = salvageable penumbra!
FLOW VOLUME
37.3±5.01 25.0±3.82 13.3±3.75 1.78±0.30 2.15±0.43 1.12±0.37
sensitivity=97.0%
CBFxCBV specificity=97.2%
accuracy=97.1%
for CBFxCBV and
subsequent stroke
threshold=31.3
Murphy, B. D. et al. Radiology 2008;247:818-825 Murphy, B. D. et al. Radiology 2008;247:818-825
5

6. Figure 3: Scatterplot shows mean CBV versus mean CBF in penumbra and infarct regions in patients with acute stroke and
confirmed recanalization at 24 hours (dashed line represents CBF×CBV = 8.14)
- 40 patients, median NIHSS=16, 19 received iv-tpa
- compared initial CTP/CTA and day #3 postop MRI/MRP
- reperfusion defined as normalization of ≥80% area with increased MTT
Murphy, B. D. et al. Radiology 2008;247:818-825
CTP parameters can predict hemorrhage
rCBF prediction of symptomatic ICH
following IA treatment for MCA occlusion
Regions with infarction (based upon DWI+ADC) at day #3 compared with CBV maps
on initial CTP → in hypoperfused areas ( ↓↓CBF, ↑↑MTT), does CBV predict
eventual infarction?
CBV Low Normal High
~ 13 ml
per 100g/min
With reperfusion 97% (go on to 41% (go on to 3% (go on to
infarct) infarct) infarct)
No reperfusion 94% (go on to 63% (go on to 94% (go on to
infarct) infarct) infarct) ~ 1/3 MCA
territory
Gupta 2006 Stroke 37:2526
Stroke Algorithm
Acute Stroke
CTP in posterior circulation!
CTA / CTP
0-3 hr >3 hr
CBF CBV MTT DWI
large vessel occl. (ICA, M1/M2, A1, VA/BA) large vessel occl. (ICA, M1/M2, A1,VA/BA)
large ischemic penumbra > infarct large ischemic penumbra > infarct
large stroke (NIHSS≥10) large stroke (NIHSS≥10)
yes no yes no
no acute thrombolysis,
IA Tx ± bridging IV tPA IV tPA IA Tx
later medical or surgical
stroke prophylaxis
6

7. SUMMARY
CTP is available and powerful:
Transit time = very sensitive (but not specific)
Flow = penumbra plus core
Volume = penumbra vs core (collateral supply)
preserved → penumbra (still salvageable)
decreased → core (dead)
CBF/CBV = crude “risk/reward” ratio
onset often unclear → CT perfusion = more accurate
physiological data
perfusion beats onset
POD#1 DWI: frontopolar, caudate, basal ganglia infarcts (predicted by CTP), but POD#1 FLAIR: small
large LMCA territory salvaged caudate head, basal
ganglia, frontopolar
infarcts
POD#2 CT
Case example:
83 yo male
acute right hemisphere stroke
left plegic, R gaze preference, L facial droop, dysarthric
NIHSS > 10
last normal > 14hrs ago
past medical history = paroxysmal atrial fibrillation
(discovered on this admission)
7

8. Emergency thrombectomy and lytics → inferior division open, residual clot in superior division
balloon angioplasty → superior division now also open
CT perfusion:
Low CBF but preserved
CBV → stroke is still
salvageable.
preop CBF preop CBV
residual
clot
Pre Post
preop CBV
preop CBF
INITIAL CTP:
-Very low blood flow
Case example:
-Very slow blood flow
-Preserved blood volume
33 yo female
-BUT: > 4hrs onset
acute right carotid stroke
CBF TTP CBV
left hemiplegia, facial droop, dysarthria, hemianopia,
neglect, decreased left body sensation, drowsy, fixed gaze
deviation to right.
NIHSS = 16
onset > 4 hrs
past medical history = smoker, oral contraceptive pills
8

9. Complete right internal carotid artery occlusion → no intracranial blood flow microcatheter run shows distal blood vessels remains patent
MRI
few
days
MERCI thrombectomy opens distal carotid and proximal middle cerebral artery, later…
balloon angioplasty opens distal middle cerebral artery
Mid-BA occlusion
Case example:
76 year old female
Found 2:30 am at outside institution with stroke, onset
unknown
Rapidly transferred to tertiary-care institution.
When seen, unable to move anything except eyes
rapidly loosing consciousness → crash intubated in ED
NIHSS = 30
9

10. Access is going to be tough!!!
Big Problem…
m
ar
m
ar
Bigger Problem…?
Pooled NASCET, ECST, VA309 results Lancet 2003,361(9352):107
Case example #1:
hyperdense sign
70 yo male
acute LMCA stroke
driving → swerved off road → min. responsive on scene
right plegic, aphasic, fixed gaze to left in ED
NIHSS = 22
onset <1.5 hrs
PMH = HTN, NIDDM, dyslipidemia, atrial flutter, on ASA
10

11. CBV reduction matches
reduction in CBF → no
collateral reserve, no
penumbra, infarct already
well established.
CBF CBV TTP
13.6 x 0.9 = 12.2
Case example #5:
70 yo male
acute RMCA stroke
initial NIHSS=12 in ED, worsened to > 18 → intubated
onset > 6 hrs
PMH = MI, CABG, PVD, HTN, NIDDM, previous L parietal
subcortical stroke
CTP (pre)
CT (pre)
CBF CBV TTP
11

12. Treatment:
Angio = RMCA bifurcation occlusion, ant. temporal open
Retavase 2mg M1
Retavase 1mg M2inf
wire both M2’s
Merci M2sup x2 Pre Post
CT (POD#1)
Outcome:
TIMI-3 M1/M2’s
distal branch of inferior M2 remained occluded
R basal ganglia ICH, R parietal infarct
rest of MCA territory spared
discharged 17 days later to rehab, NIHSS=16
return w/urosepsis one month later → no sig improvement
CT 44 days later…NIHSS still 16.
CTP keypoints:
1. TTP/MTT is very sensitive – but not specific
2. CBV distinguishes infarction vs. ischemic penumbra (dead vs. salvageable brain)
3. Areas at risk for hemorrhage post-thrombolysis can be predicted
4. Crude risk/benefit ratio = CBV / CBF deficit
Bottom line = physiological imaging is real and powerful…CTP does not lie!
12

13. SUMMARY
CTP is available and powerful:
Transit time = very sensitive (but not specific)
Flow = penumbra plus core
Volume = penumbra vs core (collateral supply)
preserved → penumbra (still salvageable)
decreased → core (dead)
CBF/CBV = crude “risk/reward” ratio
onset often unclear → CT perfusion = more accurate
physiological data
perfusion beats onset
13