The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital - DENMARK
Imaging of Transient Ischemic Attack
and Stroke
Leif Østergaard
MD, MSc, PhD, DMSc, Director, Professor
Center of Functionally Integrative Neuroscience
Department of Neuroradiology
Århus University Hospital
Overview
• MRI Techniques
Detecting hemorrhagic strokes: T2* MRI
Detecting acute ischemic lesions: Diffusion MRI
Detecting tissue at risk of infarction: Perfusion MRI
• Predicting patient outcome
Predicting stroke after TIA
Predicting infarct growth in acute stroke
• The use of MRI in acute stroke management
Is it feasible?
Does it make a difference to our patients?
Is it cost-effective?
• Current Research: Overcoming knowledge barriers
Turning large databases into clinical decisions and better care
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
Imaging TIA – and Stroke
Diffusion MRI detects early ischmic lesions
11 min pre-stroke
11 min post-stroke
3h post-stroke
24 h post-stroke
78 year old female
imaged 2 hours after
brief TIA episode.
Treated with rtPA
Hjort et al. Ann Neurol. (2005)
Acute MRA
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
Acute MTT
Ischemic stroke:
Who to treat with rtPA?
Infarct growth from 5 hours to 5 days
ICH post rtPA
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
Who to treat?
How to predict infarct growth?
Normal
autoregulation
DWI lesion
Percent Change
Tissue
Death
64 y.o. female
5.5 hours
after onset of L leg
weakness
ACA territory
MTT
MTT
1994
Adapted from Powers Powers
et al. (1994)
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
CBF
CBV
Diffusion - Perfusion Mismatch highlights tissue at risk.
≥ 90 % risk of
Infarct growth
Mismatch
T2
DWI
Sorensen et al Radiology 1999
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
rMTT
5-day
followup DWI
78 y.o. F 3 hours after onset of aphasia
Mismatch prevalence
Beyond 3 hours:
MRI Tissue Clock
Darby et al Stroke. 30:2043-52 (1999)
Acute – before tPA
At risk
NIHSSS = 14
M1 MCA occlusion
2 hours post tPA
MTT
DWI
T2 after 3 months
NIHSS = 0
MRS = 0
NIHSSS = 3
Niels Hjort, Christine Sølling, Mahmoud Ashkanian
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
62 year old female with acute left hemisensory
stroke is treated by rtPA
Acute DWI
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
DWI 2 hours after rtPA
DWI 24 hours after rtPA
•
•
TIA patients: 35% have DWI lesions, 33% have PWI lesions; 16% both
Combined 51%; mostly in ’culprit’ hemisphere
Mlynash et al. Neurology. 2008 Dec 17. [Epub ahead of print]
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
Predicting stroke after TIA
• ABCD2 and DWI (N=601/25)
Adding MRI and clinical data increases
AUC from 66% to 81% in predicting
stroke/no stroke within 1 week
Ay et al. Stroke. 2009;40:181-6
• ABCD2 DWI, LAA and AF (N=343/5/10)
Hazard ratios
•
•
•
•
ABCD(2) > 5: 10.1
DWI: 8.7
LAA 3.4
AF N.S.
Calvet et al. Stroke. 2009;40:187-92
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
Does advanced MRI work
in real life???
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
Study design
h
År
us
n
De
Area with 600 000 inhabitants
k
ar
m
New center – rtPA from April 2004
MR-project in daytime, weekdays - Otherwise CT
Prospective rtPA database from 2004-2006
Data:
• Demographics
• Time data
• Imaging data
• Outcome data
Implementation of:
• Stroke code. Fast track
• Stroke admission room
• Stroke MRI training
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
Study design
Onset-Needle-Time (ONT) : Max 3h
Door-to-Needle-Time (DNT) : Goal 60 min
Decision time
Onset-Door
Assessment
Clinical criteria:
18-80 years
NIHSS 1-25
NINDS criteria
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
MRI
Imaging criteria
No ICH (T2*)
Ischemic lesion
(DWI, PWI)
Needle-Time
rtPA
0.9 mg/kg
•
•
•
•
•
Århus Study
2004-2006
174 Referred
142 MRI
73 ischemic infarcts
40 received iv-rtPA (95 treated per mio.)
Why did 32 patients not undergo MRI?
13 not indicated
4 metal implants (pacemaker, Hoffman's app)
7 anatomy (weight, positioning)
4 unstable clinical condition
2 patient consent (claustrophobia)
2 technical problems
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
10.5 %
Results – Time data
MRI did not delay treatment compared to CT
MR
n=40
CT
n=17
68,5
64
69
NIHSS
10
9
12
"Onset-door-time"
82
105
65
"Door-imaging-time"
26
30
25
"Imaging"
25
10
5
"Onset-Imaging-report"
140
140
"Decision-time"
13
24
DNT "Door-to-needle"
70
66
68
ONT "Onset-to-needle"
157
160
145
Age
Sølling et al. Acta Neurol Scand. 2008 Dec 29.
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
SITS-MOST*
n=6483
* Wahlgren, The Lancet, 2007
Decision making
We treated 40 patients: MRI potentially influenced decisionmaking in 24 referred patients:
In favour of rtPA
2 patients thrombolysed despite seizures
• 9 patients with NIHSS < 5 (DWI +/- mismatch)
•
Often excluded
in CT based
studies
Against rtPA
• 6 patients with large infarctions (but NIHSS within limit < 25)
• 7 patients with NIHSS > 4 had no DWI lesions (stroke mimics!)
Sølling et al. Acta Neurol Scand. 2008 Dec 29.
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
All
Mild
0,0
Moderate
Severe
NIHSS>15
NIHSS 8-15
mRS 0-2: for NIHSS >14
0,4
0,6
0,5
Saver, Stroke, 2007
0,0
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
NINDS tPA
Sølling et al Cerebrovasc Dis. 2009;27:223-229.
Århus CT
0,1
Århus MR
0,2
Århus all
0,3
0,4
0,3
0,2
0,1
0,0
Århus all
0,5
NINDS placebo
mRS 0-1: for NIHSS 8-14
NINDS placebo
0,0
NINDS
placebo
mRS 0: for NIHSS <8
0,1
NINDS tPA
0,1
NINDS tPA
‘Good outcome’:
0,2
Århus CT
0,2
Århus MR
(sliding dichotomy)
Århus CT
0,3
NINDS placebo
0,3
NINDS tPA
0,4
Århus CT
0,4
Århus MR
0,5
Århus MR
NIHSS<8
0,5
Århus all
Outcome within
severity subgroups
All
Århus all
Outcome
Does acute imaging
only help those who get rtPA?
• Prospective registration of 800 “stroke mimics” at our stroke unit
Stage I: Before implementation of tPA
Stage II: During implementation (MR-project)
Stage III: After full implementation
• Data
Baseline clinical data (age, gender, neurological signs (SSS))
Time data (admission, imaging, discharge)
Discharge-diagnoses (ICD-10 codes)
• Analysis: Predictors for Length-of-Stay (LOS)
• Estimate of economic implications
Sølling et al. Cerebrovasc Dis. 2009;27:60-6.
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
III Results
Stage I : Before tPA
Stage II: During MR-project
Stage III: After full implementation of tPA
Stage III:
LOS
significantly
reduced after
implementation
of tPA
Sølling et al. Cerebrovasc Dis. 2009;27:60-6.
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
Acute referral organization with MRI
Acute stroke organization
Immediate imaging
Fast diagnostic evaluation
Faster discharges (50% LOS reduction) – related to acute MRI
Thrombolysis is cost-effective*.
In addition, improved management of non-stroke patients may also
contributes to the cost-effectiveness of tPA treatment (estimated 30%
cost reduction)
Sølling et al. Cerebrovasc Dis. 2009;27:60-6.
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
*Ehlers, Stroke, 2007
Flaskehalsen: For mange data
1400 images
2 minutes
Experience from 1000 patients
1 million neurons die every minute!
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
Niels Hjort, Christine Sølling, Mahmoud Ashkanian
Stroke prediction model based on expertclassified database: Joint EU project I-Know
• Model based on expert-classified database (120 patients)
• Model seeks to separate final outcome (infarct/salvaged) in Ndimensional space (voxel-by-voxel image intensity and available
clinical/treatment data) across all patients
• Resulting model yields infarct risk map in ’unknown’ patient based on
acute image and clinical data.
Østergaard et al Current Opinions Neurol 2009
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
Diagnostic Support System
Expert diagnosis based on database - Everywhere
Århus University Hospital
111111-1112
John Doe
Infarct Risk
100%
Risik factors
Diabetes
Hypertension
Based on
120 patients
30%
EPR
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
Latest
Current beta-version
•
•
•
•
•
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
Automated data analysis
Mismatch segmentation
Volume calculations
Best-case prediction:
Reperfusion (N=32)
Worst-case prediction
No reperfusion (N=29)
Take-home: Overview
• MRI Techniques
Detecting hemorrhagic strokes: T2* MRI
Detecting acute ischemic lesions: Diffusion MRI
Detecting tissue at risk of infarction: Perfusion MRI
• Predicting patient outcome
Predicting stroke after TIA MRI and clinical data
Predicting infarct growth in acute stroke MRI (and CT)
• The use of MRI in acute stroke management
Is it feasible? Yes – and as fast as conventional CT!
Does it make a difference to our patients? Yes – better selection!
Is it cost-effective? Yes!
• Current Research: Overcoming knowledge barriers
Turning large databases into clinical decisions and better care
Clinical Decision Support Systems may help advanced
decentralized treatment
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
I-Know Partners
Contact:
www.i-know-stroke.eu
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
Leif Østergaard, MD, PhD, MSc, DMSc
Professor, I-Know Project Coordinator
Aarhus University Hospital - DENMARK
[email protected]
Diffusion Weighted Imaging
Changes in Ischemia
Cat br ain - MCA occlusion
Hindrance Restriction Barriers
ATP-depletion
Na+-K+ pump
Cytotoxic edema
Increased extracellular tortuosity
Hindrance of water movement
ADC decreases (0-5 days) = bright DWI
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
Moseley M.E , et al. 1990
Apparent Diffusion Coefficient (ADC)
• Vary diffusion weighting b: S=exp (-bADC)
Important w. ‘T2-shine through’
How old is the lesion?
• Cytotoxic edema (5-6d)
• Vasogenic edema (> 7 days)
b
Dw- MRI
S
ADC map
ADC
b
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
Courtesy Drs Bihan, Oppenheim
Results - Outcome
• 83 tPA after MRI
• 27 tPA after CT
• Symptomatic hemorrhages (<2%)
Theoretical risk: 5- 8%, SITS-MOST: 2 %
• Asymptomatic hemorrhages 20%
Found at follow up
• Mortality within 3 months (6,3%)
SITS-MOST: 15%
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
Continous efforts reduces DNT
Aarhus
Denmark
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
Ruling out ICH by MRI
47 y.o. male, known HT: MRI after 5½ hours
• T2*
DWI
DWI ’rim’ phenomenon, signal loss on T2*
The Hemorrhage and Early MRI Evaluation
(HEME) study. MRI < 6 h after onset. MRI:
1.5 T, T2* GRE, DWI b=0 and b=1000.
Kidwell, JAMA 2004
The Danish National Research Foundation’s
Center of Functionally Integrative Neuroscience
Aarhus University / Aarhus University Hospital
T2*