Patient Selection using CT Perfusion (CTP) Imaging Improves ...

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Patient Selection using CT Perfusion (CTP) Imaging Improves ...

Patient Selection using CT Perfusion

(CTP) Imaging Improves

Effectiveness of Stroke Thrombolysis

in the 0-4.5 Hour Time Window

Dulka Manawadu, Shankranand Bodla, Laszlo

Sztriha, Jozef Jarosz, Lalit Kalra

Dept. of Clinical Neurosciences King’s College London


Introduction

• Thrombolysis within 4.5 hours is highly effective

for Acute Ischaemic Stroke (AIS)

• NCCT brain scan cannot identify potentially

salvageable tissue

• Only 10-15% AIS patients treated as expected

gains compared with treatment risks are unclear

• Physiological imaging may quantify salvageable

brain tissue, but utility is controversial


Physiological Imaging

Patient selection using PWI/DWI MR imaging

may improve outcomes

• MR imaging limited by access, expertise, time

and patient factors

CTP with NCCT at initial assessment is simpler,

widely available but also has limitations

• It is unknown whether demonstration of a CTP

mismatch prior to thrombolysis in the 4.5h time

window is associated with a better outcome


Aims and Objectives

Hypothesis

• Functional outcomes will be better in AIS

patients with CTP mismatch thrombolysed in 0-

4.5 h compared to those with no deficit or

mismatch

Objectives

• To compare sICH, mRS and mortality in patients

with and without CTP mismatch

• To assess the independent effects of CTP

mismatch on patient outcomes


Methods

Data extracted from a registry of thrombolysed patients

• Unselected consecutive patients, all ages, CTP imaging,

thrombolysed 0-4.5h

• Age, sex, vascular risk factors, stroke aetiology, premorbid

mRS, BP, glucose, NIHSS score

Outcome measures

• 24h: NIHSS and ΔNIHSS scores

• 72h: ICH, sICH

• 3 months: mRS score, mortality

• Functional outcomes by certified assessors masked to

imaging


CTP Imaging

• 16-slice CT scanner, CTP immediately after NCCT

• Power injection of 50 ml of Ominpaque at 4 ml/s.

• Two 10-mm slices: basal ganglia, superior to orbits

• Cerebral blood volume (CBV), cerebral blood flow (CBF)

and mean transit time (MTT)

Assessment of Perfusion

• 2 trained assessors masked to outcomes

• Semi-quantitative visual technique using ASPECTS 1

• Areas with normal CBV and MTT =1, impaired areas =0

• Mismatch = CBV ASPECTS - MTT ASPECTS (0-10)

• ASPECTS Mismatch 2 = volumetric mismatch 100% 2

1. Lin et al, AJNR 2008;29:931–36; 2.Lin et al. Neuroradiology. 2009;51:17-23.


Baseline Characteristics

No mismatch

N=65

Mismatch

N=100

Mean (SD) age in years 72.6 (14.3) 69.8 (16.3) 0.26

Male (%) 32 (49%) 53 (53%) 0.64

Hypertension (%) 30 (46%) 67 (67%) 0.009

Diabetes (%) 9 (14%) 13 (13%) 1.00

Atrial fibrillation (%) 16 (25%) 19 (19%) 0.44

Mean (SD) baseline SBP (mm Hg) 148 (24) 148 (25) 0.92

Mean (SD) baseline DBP (mm Hg) 87 (15) 80 (15) 0.003

Mean (SD) baseline glucose (mmol/l) 6.5 (1.9) 6.5 (2.4) 0.95

Mean (SD) baseline NIHSS (SD) 13.6 (6.3) 12.1 (6.6) 0.16

HMCAS 31 (48%) 23 (23%) 0.001

Stroke Aetiology 0.010

Large artery atherosclerosis 7 (11%) 33 (33%)

Cardioembolic 32 (49%) 27 (27%)

Lacunar 4 (6%) 8 (8%)

Rare 3 (5%) 6 (6%)

Mixed/undetermined aetiology 19 (29%) 26 (26%)

P


Clinical Outcomes

No mismatch

N=65

Mismatch

N=100

Mean (SD) NIHSS at 24 hours 11.5 (9.5) 7.2 (6.9) 0.001

Mean (SD) change in NIHSS at 24

h

-1.8 (8.1) -4.9 (5.8) 0.006

Any ICH (%) 13 (20%) 12 (12%) 0.19

SICH (%) 1 (1.5%) 1 (1%) 1.00

mRS 0-1 at 3 months (%) 12 (19%) 38 (38%) 0.009

mRS 0-2 at 3 months (%) 22 (34%) 55 (55%) 0.010

Mortality at 3 months (%) 19 (29%) 16 (16%) 0.08

P


Age 80 years, NIHSS≥5

Baseline characteristics

No mismatch

N=44

Mismatch

N=76

Mean (SD) age in years 75.8 (12.3) 64.3 (14.8) 0.56

Male (%) 25 (57%) 46 (61%) 0.69

Hypertension (%) 17 (39%) 46 (61%) 0.017

Mean (SD) SBP 143 (20) 147 (25) 0.58

Mean (SD) DBP 87 (13) 80 (15) 0.021

Mean (SD) NIHSS 12.9 (6.3) 11.0 (6.1) 0.11

HMCAS 19 (43%) 17 (22%) 0.023

Outcomes

Mean (SD) NIHSS at 24 h 10.7 (9.5) 6.2 (6.1) 0.002

Mean (SD) ΔNIHSS at 24

h

-2.0 (8.2) -5.0 (5.1) 0.019

Any ICH (%) 8 (18%) 9 (12%) 0.35

SICH (%) 1 (2.3%) 0 (0%) 0.19

mRS 0-1 at 3/12 (%) 9 (21%) 34 (45%) 0.008

mRS 0-2 at 3/12 (%) 18 (41%) 45 (59%) 0.04

Mortality at 3/12 (%) 9 (20%) 10 (13%) 0.29

P


CTP mismatch and mRS shift

mismatch

no mismatch

6

16

12

15

22

mRS at 3 months

17

17

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

mRS 0 mRS 1 mRS 2 mRS 3 mRS 4 mRs 5 mRS 6

Outcome All ages and all

NIH

9

16

11

9

P= 0.022

4

29

16

Adjusted for age and

baseline NIHSS score

mRS 0-1 at 3/12 2.7 (1.3-5.7) 3.1 (1.3-7.4)

mRS 0-2 at 3/12 2.4 (1.3-4.6) 2.1 (1.01-4.5)


Predictors mRS 0-2 at

3/12

Age 0.95 (0.92-0.98)

p=0.003

Baseline NIH 0.91 (0.85-0.98)

p=0.013

Prognostic Indicators

Death NIH at 24

hours

1.1 (1.01-1.10)

p=0.015

1.1 (1.01-1.20)

p=0.020

HMCAS 3.5 (1.3-9.1)

p=0.011

B=0.08

p=0.034

B=0.71

p=0.0001

CTP mismatch B=-3.4

p=0.003

Variables entered:

Δ NIH

B= -0.08

p=0.037

B= -0.29

p=0.006

B=3.5

p=0.003

Age, sex, HT, DM, AF, pre-morbid mRS, SBP, DBP, glucose, baseline NIHSS,

carotid stenosis, HMCAS and CTP mismatch


Limitations

• Registry based study, inadvertent bias may

influence results

• No outcome data for non-thrombolysed patients

after CTP

• Carotid stenosis may have affected CTP

characteristics in favour of mismatch

• Mismatch and outcomes may be adversely

affected due to inclusion of older patients

• Assessment of mismatch is controversial


Conclusions

Patient selection on the basis of CTP imaging is

feasible in routine clinical settings

• Existing simple algorithms can reliably identify

patients with significant mismatch

• Demonstration of mismatch may improve

outcomes of stroke thrombolysis even within 4.5

hours of symptom onset

• Prospective trials on the role of multimodal CT

imaging for patient selection in AIS are justified


Perfusion Thresholds

CT Perfusion 2.6.9 software (GE Healthcare)

• CBV (Cerebral Blood Volume): 0-10 ml/100 g

• CBF (Cerebral Blood Flow): 0-100 ml/100 g/sec

• MTT (Mean Transit Time): 0-15 s

• TTP (Time to Peak): Not used at KCH

Maps depend upon processing methods, impressive differences in volumes

Different systems have different thresholds

Maps vary because of hardware and software considerations

Incomplete area of coverage


CTP criteria for penumbra

– CBF 20ml/100g/s oligemia

– CBV 8 sec severe ischaemia

4-8 sec at risk, reversible

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