Quantitative MR Imaging of Acute Stroke

Risto Kauppinen

• Unambiguous diagnosis of acute ischemia by MRI (1990)

• Monitoring expansion of ischaemic damage by MRI (1991)

• rtPA introduced as a therapeutic agent (1996)

• Availability of CT scans for stroke A & E (since mid 90s)

• [Shift to 3T MR scanners in Clinical Radiology (since 2005)]

• [Computing power has increased and become cheaper]

Acute Stoke: Advances since 1990

DWI (45 min) T2w (65 min)

MRI: translation to clinic

DWI (45 min) T2w (65 min)

MRI: translation to clinic

Kuharchyck et al. 1991Warach et al. 1992

Griffin JL et al. Cancer Res 63:3195, 2003

Quantitative MRI (qMRI)

Each pixel in an image is represented by a physically

meaningful number

- Relaxation times (T1, T2, T1), ADC, haemodynamics etc.

- Normative values

- Requires acquisition of multiple data points

Griffin JL et al. Cancer Res 63:3195, 2003

qMRI in clinical settings

Griffin JL et al. Cancer Res 63:3195, 2003

qMRI in clinical settings

Griffin JL et al. Cancer Res 63:3195, 2003

Expectations from imaging in clinics

Radiol Clin N Am 49:1-26 (2011)

Goals in acute stroke management

• Rescue the penumbra

by maximising use of available

treatment strategies

• Patient –specific management

• Guide patient triaging

for investigational therapies

DWI ADC image

qMRI: Diffusion MRI in acute ischaemia

-Catastrophic drop in CBF-Energy failure-Depolarisation-Disturbance in water homeostasis

Grohn et al. J Cereb Blood Flow Metab 20: 316, 2000

ADC and Blood FlowIschaemia compromised normal blood flow

Grohn et al. J Cereb Blood Flow Metab 20: 316, 2000

ADC and Blood Flow

ADC/Trace decrease in acuteischaemiais not an ON-OFF event

motivation for qMRI

Ischaemia penumbra normal blood flow

qMRI: pixelwise histogram of ADCs

VOLUME

ADC

Normal

Ischaemic

Ischaemic+compromised

ADC map

qMRI: pixelwise histogram of ADCs

VOLUME

ADC

Normal

Ischaemic

Ischaemic+compromised

ADC map

qMRI: Potentials of (q)ADC

• State of tissue beyond perfusion-diffusion mismatch as assessed by volume (mis)match• Degree of ischaemia in parenchyma• Guide patient selection for reperfusion therapy

qMRI: Potentials of (q)ADC• State of tissue beyond perfusion-diffusion mismatch as assessed by volume (mis)match• Degree of ischaemia in parenchyma• Guide patient selection for reperfusion therapy

• Image pixels are either absolute T1 or T2 relaxation times

• Absolute T1/T2 are much more sensitive to parenchymal alterations than either T1w or T2w images

MR relaxometry

T1 and T2 in acute stroke

24 h afterischaemia

Dav

T1

T2

25 min ofreperfusion

40

60

80

100

120

T1 (m

s)

20

40

60

80 T2 (m

s)

0.5

0.6

0.70.8

0.9D

av ( 10-3 m

m2/s) 0.5

0.6

0.70.8

0.9

Dav ( 10

-3 mm

2/s)

40

50

60

7080

90

T1 (m

s)

45

55

65

75

T2 (m

s)

35 min ofhypoperfusion

45 min of ischaemia

Gröhn O.H.J. et al. MRM 42: 268, 1999

Multiparametric qMRI in acute ischaemia

-6

-4

-2

0

2

4

T2 (m

s)

-0.5-0.4-0.3-0.2-0.1

00.10.2

Dav

(10

-3 m

m2 /

s)

Time post-ischaemia (min) Time post-ischaemia (min)

8020 40 60

***

*

**

*

*

20 40 60 80

****

**

***

Cortex1Cortex2

Putamen

Areas analysed:

Gröhn O et al. JCBFM 18:911 (1998)

Acute ischaemiaTransition toirreversible

Vertebral arteryocclusions

2 days later

remotecontrolledgradualoccluder

Remote controlgraded occlusion

Time of Stroke Onset by MRI

Jokivarsi et al. Stroke 41; 2335-40, 2010

Vertebral arteryocclusions

2 days later

remotecontrolledgradualoccluder

Remote controlgraded occlusion

a) Controllable forebrain ischaemiab) Cortical hypoperfusion (’misery perfusion’)c) Middle cerebral artery (MCA) occlusion

Time of Stroke Onset

Jokivarsi et al. Stroke 41; 2335-40, 2010

Vertebral arteryocclusions

2 days later

remotecontrolledgradualoccluder

Remote controlgraded occlusion

a) Controllable forebrain ischaemiab) Cortical hypoperfusion (’misery perfusion’)c) Middle cerebral artery (MCA) occlusion

Time of Stroke Onset

Jokivarsi et al. Stroke 41; 2335-40, 2010

Vertebral arteryocclusions

2 days later

remotecontrolledgradualoccluder

Remote controlgraded occlusion

a) Controllable forebrain ischaemiab) Cortical hypoperfusion (’misery perfusion’)c) Middle cerebral artery (MCA) occlusion

Time of Stroke Onset

Jokivarsi et al. Stroke 41; 2335-40, 2010

Calibration for humanbrain parenchyma nottrivial

Absolute T2 in Acute Stroke

Siemonsen et al. Stroke 40: 1612, 2009

<3 hours of stroke: qT2

@1.5T

Cut-off 7.5msSensitivity 0.824Accuracy 0.794ROC 0.757(ROC(ADC) 0.635)

T1 in Acute Stroke

Very early increase in T1

in Str by 63±16ms (+6%)

Able to discriminate lesionexpansion and non-damagingcortex, despite similar CBFvalues in early stroke

30min

2.5h

24h

Multi-parametric MRI of Acute Stroke

Jokivarsi et al. MRM under revision

-10 %

-5 %

0 %

5 %

10 %

15 %

20 %

25 %

30 %

S1 S2 C1 C2 C3

T2

TP1

TP2

TP3

TP4

TP5

TP6

C‡‡‡‡ ‡ ‡†‡ ‡ †‡‡ ‡ ‡‡ ‡ †

-10 %

-5 %

0 %

5 %

10 %

15 %

20 %

25 %

30 %

S1 S2 C1 C2 C3

T1

TP1

TP2

TP3

TP4

TP5

TP6

B‡‡‡‡‡ ‡ ‡‡‡‡‡ ‡ ‡‡‡‡‡ ‡ ‡‡‡‡‡ ‡ ‡‡‡‡‡ ‡

-10 %

-5 %

0 %

5 %

10 %

15 %

20 %

25 %

30 %

S1 S2 C1 C2 C3

RAFF

TP1

TP2

TP3

TP4

TP5

TP6

D‡‡† ‡ †† ‡†† †

-10 %

-5 %

0 %

5 %

10 %

15 %

20 %

25 %

30 %

S1 S2 C1 C2 C3

T1

TP1

TP2

TP3

TP4

TP5

TP6

A‡‡‡‡‡ ‡ ‡‡‡‡‡ ‡ ‡‡‡‡‡ ‡ ‡‡‡‡‡ ‡ ‡‡‡‡‡ ‡

S1

S2

C1

C2

C3

Multi-parametric MRI of Acute Stroke

Jokivarsi et al. MRM under revision

-10 %

-5 %

0 %

5 %

10 %

15 %

20 %

25 %

30 %

S1 S2 C1 C2 C3

T2

TP1

TP2

TP3

TP4

TP5

TP6

C‡‡‡‡ ‡ ‡†‡ ‡ †‡‡ ‡ ‡‡ ‡ †

-10 %

-5 %

0 %

5 %

10 %

15 %

20 %

25 %

30 %

S1 S2 C1 C2 C3

T1

TP1

TP2

TP3

TP4

TP5

TP6

B‡‡‡‡‡ ‡ ‡‡‡‡‡ ‡ ‡‡‡‡‡ ‡ ‡‡‡‡‡ ‡ ‡‡‡‡‡ ‡

-10 %

-5 %

0 %

5 %

10 %

15 %

20 %

25 %

30 %

S1 S2 C1 C2 C3

RAFF

TP1

TP2

TP3

TP4

TP5

TP6

D‡‡† ‡ †† ‡†† †

-10 %

-5 %

0 %

5 %

10 %

15 %

20 %

25 %

30 %

S1 S2 C1 C2 C3

T1

TP1

TP2

TP3

TP4

TP5

TP6

A‡‡‡‡‡ ‡ ‡‡‡‡‡ ‡ ‡‡‡‡‡ ‡ ‡‡‡‡‡ ‡ ‡‡‡‡‡ ‡

S1

S2

C1

C2

C3

30 min of ischaemia

24 hours of ischaemia

Focus on endogenous metabolites

qMR spectroscopy (qMRS)

‘1H MRS neurochemical profile at 3T’

Wilson et al. Magn Reson Med 65: 1 (2011)

State-of-the-art 1H MRS

NAA

Cr

(lac)

1H MRS Metabolites in Stroke

Van der Toorn et al. MRM 32: 865 (1994)

Cr NAA

Lac

1H MRS in Acute Stroke

Saunders et al. JMRI 7: 1116 (1997)

Reduced NAA: clinical stroke syndrome, more extensive infarction, severe drop in blood flow, presence of lactate

Increased lactate: large infarcts and reduced NAA

Reduced NAA: clinical stroke syndrome, more extensive infarction, severe drop in blood flow, presence of lactate

Increased lactate: large infarcts and reduced NAA

Low NAA and high lactate predicted expansion of DWI lesion

• Potentials to provide clinically important data from a single exam

• Objective assessment of tissue status (early on)

• Potentially guides clinical management of patients

• Aids to maximise use of available therapies

• Allows patient –specific treatment protocols

qMR in acute stroke: Conclusions

• Standard clinical hardware

• Requires expertise and commitment

• Standardised MR protocols

• Regular QA according to appropriate procedures

• Automated on-line data processing

• Computer-assisted decision making tools

qMRI/S in clinical setting

Stroke Management in the 21st Century

1. Active prevention2. Thrombolysis3. Minocyclin4. Hematopoetic growth factors5. Hypothermia6. Remote preconditioning

• Application specific scanners– Lower capital costs– Lower running costs– Increased availability at A&E– Faster through-put– Improved data quality

• Tissue status assignment for therapeutic procedures• Improving overall outcome of stroke patients

MR in Evaluation of Acute Stroke Patients in 2020s