1. Quantitative MR Imaging of Acute Stroke
Risto Kauppinen

2. Acute Stoke: Advances since 1990
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]

3. MRI: translation to clinic
DWI (45 min) T2w (65 min)

4. MRI: translation to clinic
DWI (45 min) T2w (65 min)
Kuharchyck et al. 1991
Warach et al. 1992

5. Quantitative MRI (qMRI)
Each pixel in an image is represented by a physically
meaningful number
- Relaxation times (T1, T2, T1r), ADC, haemodynamics etc.
Normative values
- Requires acquisition of multiple data points
Griffin JL et al. Cancer Res 63:3195, 2003

6. qMRI in clinical settings
Griffin JL et al. Cancer Res 63:3195, 2003

7. qMRI in clinical settings
Griffin JL et al. Cancer Res 63:3195, 2003

8. Expectations from imaging in clinics
Griffin JL et al. Cancer Res 63:3195, 2003
Radiol Clin N Am 49:1-26 (2011)

9. Goals in acute stroke management
Rescue the penumbra
by maximising use of available
treatment strategies
Patient –specific management
Guide patient triaging
for investigational therapies

10. qMRI: Diffusion MRI in acute ischaemia
DWI ADC image
-Catastrophic drop in CBF
-Energy failure
-Depolarisation
-Disturbance in water
homeostasis
Change in temperature and changes in relaxation times might also influence the estimation of pH from ΔPTR.

11. ADC and Blood Flow Ischaemia compromised normal blood flow
Grohn et al. J Cereb Blood Flow Metab 20: 316, 2000

12. ADC and Blood Flow ADC/Trace decrease in acute ischaemia
Ischaemia penumbra normal blood flow
ADC/Trace decrease
in acute
ischaemia
is not an ON-OFF event
motivation for qMRI
Grohn et al. J Cereb Blood Flow Metab 20: 316, 2000

13. qMRI: pixelwise histogram of ADCs
ADC map
Normal
Ischaemic +
compromised V O L U M E

14. qMRI: pixelwise histogram of ADCs
ADC map
Normal
Ischaemic +
compromised V O L U M E

15. 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

16. 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

17. MR relaxometry
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
Change in temperature and changes in relaxation times might also influence the estimation of pH from ΔPTR.

18. T1 and T2 in acute stroke

19. Multiparametric qMRI in acute ischaemia
24 h after
ischaemia
Dav
T1r T2
25 min of
reperfusion 40 60 80
100
120
T1r (ms) 20
T2 (ms)
0.5
0.6
0.7
0.8
0.9
Dav ( 10-3 mm2/s) 50 70 90 45 55 65 75
35 min of
hypoperfusion
45 min of
This slide summarises results from both hypoperfusion and MCA occlusion models. It becomes clear that misery perfusion without energy failure, et with negative BOLD response in T2 MRI, does not affect T1rho. I will explain why this happens little later.
In the transient MCA occlusion model we have an interesting dissociation between diffusion and T1rho MRI. In the cortical brain after occlusion diffusion recovers, however, T1rho shows elevated values in this tissue type. During the course of insult the entire MCA territory develops infarction. This is very interesting suggesting that elevated T1rho in a sign of irreversible ischaemia.
Gröhn O.H.J. et al. MRM 42: 268, 1999

20. Acute ischaemia DDav (10-3 mm2/s) DT2 (ms) Time post-ischaemia (min)
Transition to
irreversible 4
0.2
0.1 2 20 40 60 80 * 20 40 60 80
DT2 (ms)
DDav (10-3 mm2/s)
-0.1 *
-0.2 -2 * * * * ** * * *
-0.3 * -4 * **
-0.4 ** -6
-0.5
Time post-ischaemia (min)
Time post-ischaemia (min)
In fact, one can find brain areas with differing time course for T2, for instance striatal ROI displays negative BOLD in the early moments of MCA occlusion and low diffusion. T2 returns to the normal or even above it as a result of transition to irreversible ischaemia. In contrast, cortex 1 on the periphery of ischaemia remain BOLD negative for much longer time, suggesting that there is collateral flow and oxygen uptake in this tissue and perhaps this tissue type would be salvageable by therapy.
Cortex1
Cortex2
Putamen
Areas analysed:
Gröhn O et al. JCBFM 18:911 (1998)

21. Time of Stroke Onset by MRI
Vertebral artery
occlusions
Remote control
graded occlusion
2 days later
remote
controlled
gradual
occluder
We have used several animal models to test our simulations, one of them being a variant of Pulsinelli model for 4-vessel occlusion. In this model vertebral arteries are permanemtly occluded 2 day prior to controlled restriction of flow in both carotid arteries. By doing so we can get a global control decline in blood flow.
We have also used permanent hypoperfusion model in which a distal branch of MCA is occluded as well as standard thread occlusion of MCA through internal carotid aretry.
Jokivarsi et al. Stroke 41; , 2010

22. Time of Stroke Onset 2 days later remote controlled gradual occluder
Vertebral artery
occlusions
Remote control
graded occlusion
2 days later
remote
controlled
gradual
occluder
We have used several animal models to test our simulations, one of them being a variant of Pulsinelli model for 4-vessel occlusion. In this model vertebral arteries are permanemtly occluded 2 day prior to controlled restriction of flow in both carotid arteries. By doing so we can get a global control decline in blood flow.
We have also used permanent hypoperfusion model in which a distal branch of MCA is occluded as well as standard thread occlusion of MCA through internal carotid aretry.
a) Controllable forebrain ischaemia
b) Cortical hypoperfusion (’misery perfusion’)
c) Middle cerebral artery (MCA) occlusion
Jokivarsi et al. Stroke 41; , 2010

23. Time of Stroke Onset 2 days later remote controlled gradual occluder
Vertebral artery
occlusions
Remote control
graded occlusion
2 days later
remote
controlled
gradual
occluder
We have used several animal models to test our simulations, one of them being a variant of Pulsinelli model for 4-vessel occlusion. In this model vertebral arteries are permanemtly occluded 2 day prior to controlled restriction of flow in both carotid arteries. By doing so we can get a global control decline in blood flow.
We have also used permanent hypoperfusion model in which a distal branch of MCA is occluded as well as standard thread occlusion of MCA through internal carotid aretry.
a) Controllable forebrain ischaemia
b) Cortical hypoperfusion (’misery perfusion’)
c) Middle cerebral artery (MCA) occlusion
Jokivarsi et al. Stroke 41; , 2010

24. Time of Stroke Onset 2 days later remote controlled gradual occluder
Vertebral artery
occlusions
Remote control
graded occlusion
2 days later
remote
controlled
gradual
occluder
Calibration for human
brain parenchyma not
trivial
We have used several animal models to test our simulations, one of them being a variant of Pulsinelli model for 4-vessel occlusion. In this model vertebral arteries are permanemtly occluded 2 day prior to controlled restriction of flow in both carotid arteries. By doing so we can get a global control decline in blood flow.
We have also used permanent hypoperfusion model in which a distal branch of MCA is occluded as well as standard thread occlusion of MCA through internal carotid aretry.
a) Controllable forebrain ischaemia
b) Cortical hypoperfusion (’misery perfusion’)
c) Middle cerebral artery (MCA) occlusion
Jokivarsi et al. Stroke 41; , 2010

25. Absolute T2 in Acute Stroke
<3 hours of stroke: qT2
@1.5T
Cut-off 7.5ms
Sensitivity 0.824
Accuracy 0.794
ROC 0.757
(ROC(ADC) 0.635)
Siemonsen et al. Stroke 40: 1612, 2009

26. T1 in Acute Stroke Very early increase in T1 in Str by 63±16ms (+6%)30
min
2.5 h 24
Very early increase in T1
in Str by 63±16ms (+6%)
Able to discriminate lesion
expansion and non-damaging
cortex, despite similar CBF
values in early stroke
Change in temperature and changes in relaxation times might also influence the estimation of pH from ΔPTR.

27. Multi-parametric MRI of Acute Stroke
T1rho increases upon ischaemia at the ischaemic blood flow threshold, i.e. at the threshold where ATP is exhausted, lactate accumulates and diffusion failure develops.
Jokivarsi et al. MRM under revision

28. Multi-parametric MRI of Acute Stroke
30 min of ischaemia
24 hours of ischaemia S1 S2 C1 C2 C3
T1rho increases upon ischaemia at the ischaemic blood flow threshold, i.e. at the threshold where ATP is exhausted, lactate accumulates and diffusion failure develops.
Jokivarsi et al. MRM under revision

29. qMR spectroscopy (qMRS)
Focus on endogenous metabolites
Change in temperature and changes in relaxation times might also influence the estimation of pH from ΔPTR.

30. State-of-the-art 1H MRS
NAA Cr
(lac)
‘1H MRS neurochemical profile at 3T’
Wilson et al. Magn Reson Med 65: 1 (2011)

31. 1H MRS Metabolites in StrokeCr
NAA
Lac
Van der Toorn et al. MRM 32: 865 (1994)

32. 1H MRS in Acute Stroke
Saunders et al. JMRI 7: 1116 (1997)

33. Reduced NAA: clinical stroke syndrome, more extensive infarction,
severe drop in blood flow, presence of lactate
Increased lactate: large infarcts and reduced NAA

34. Reduced NAA: clinical stroke syndrome, more extensive infarction,
severe drop in blood flow, presence of lactate
Increased lactate: large infarcts and reduced NAA

35. Low NAA and high lactate predicted expansion of DWI lesion

36. qMR in acute stroke: Conclusions
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

37. qMRI/S in clinical setting
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

38. Stroke Management in the 21st Century
Active prevention
Thrombolysis
Minocyclin
Hematopoetic growth factors
Hypothermia
Remote preconditioning

39. MR in Evaluation of Acute Stroke Patients in 2020s
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
Change in temperature and changes in relaxation times might also influence the estimation of pH from ΔPTR.