1. Joshua A. Hirsch, MD DISCLOSURES Consulting Fees
Intratech Medical LTD., Medtronic CardioVascular, Inc.

2. Acute Stroke Intervention: Part 3 Imaging (basic-->advanced for triage)
Joshua A. Hirsch, MD FSIR
Albert Yoo MD
Vice Chief Interventional Care
Director : Interventional Neuroradiology/Endovascular Neurosurgery
Chief: Minimally Invasive Spine Surgery
Massachusetts General Hospital
Associate Prof: Harvard Medical School

3. Disclosures: stroke Consultant and shareholder: Intratech
Steering Committee: MERCI Registry--all honoraria donated to charity (NERF)
Co-investigator on all IA stroke studies MGH is participating in.
Some slides provided by industry
Discussion will include off label use of product

4. Stroke Physiology
After acute proximal artery occlusion, there is a characteristic progression of neuronal death
Currently, time = surrogate for the extent of brain injury
Imaging seeks to individualize treatment decisions

5. Time is Brain??? 8 HOURS POST-ICTUS
Mrn
8 HOURS POST-ICTUS
79 year old female with right hemiparesis and seizure: ICA-T occlusion

6. Time is Brain??? 2.5 HOURS POST-ICTUS
Mrn
2.5 HOURS POST-ICTUS
74 year old male with right hemiparesis and aphasia: ICA-T occlusion

7. Courtesy of Reza Hakimelahi, MD

8. Rate of neuronal loss Infarct burden = Rate of neuronal loss x Time
Distance = Rate x Time
Infarct burden = Rate of neuronal loss x Time

9. Collateral circulation
Koroshetz / Gonzalez
In :Acute Ischemic Stroke Imaging and Intervention 2006
Christoforidis AJNR 26:1789–1797, August 2005

10. Key imaging questions Is there a hemorrhage? NCCT ≥ MRI
Is there a vessel occlusion? CTA > MRA
How much is dead? DWI > NCCT (?CTA SI, ?CTP)
How much is at risk? Perfusion imaging??

11. Basic Imaging Physics
CT has one intrinsic contrast mechanism = differences in electron density
MRI can image many different physical properties of protons: density, T1 & T2 relaxation times, diffusivity
For both CT and MRI, contrast can be given to assess perfusion characteristics in the ischemic bed

12. Range of Human Tissue in HU
HU scale
-1000
water
900
air 50
-50
bone
level
window
Bone ≥ 900
Blood
Muscle = 50
Gray Matter = 40
White Matter = 30
Water = 0
Fat = -80
Lung = -300
Courtesy of Rajiv Gupta, M.D.

13. What does CT measure? HU scale bone 900 50 water -50 air -1000
water
900
air 50
-50
bone
level
window
Differences in attenuation secondary to tissue and electron density
Higher the density  brighter the object
Measured in HU and relative to H2O
Brain:
Gray matter: HU
White matter: HU

14. Noncontrast head CT scan
Gray matter:
Basal ganglia,
Cortex
White matter

15. Is there a hemorrhage?

16. Assessment of intracranial hemorrhage
HU scale
-1000
water
900
air 50
-50
bone
level
window
Higher the density  brighter the object
Acute extravascular blood is brighter than brain
Blood: HU
Brain:
Gray matter: HU
White matter: HU

17. Traditional Imaging of Acute Stroke: Non-Contrast CT
Exclude intracranial hemorrhage:
Hemorrhagic (non-ischemic) stroke
Cytotoxic edema with accumulation of water in GM strucutres decreasing their HU
Change of 4HU is visually detectable and corresponds to a change in water content of approx 1.5%
Severre ischemia with poor collateral circulation
3% increase in water content within 1 h
6% increase within 4h
Severe ischameia is detectable within 1 hour but areas with marginal cereb ral blood flow remain undetected
Vasogenic edema –
effacement of cerebral sulci
diffuse parenchumal hypodensity
Hyperdense MCA sign has high specificty but low sensitivity for an occluded cerebral artery
Extensive diffuse hyposensity on early CT scans involving over 50% of MCA territory is associated with hihgh mortality from malignant brain edema
Early ischemic changes are subtle and easily overloooked by even experienced observers
ECASS – post hoc review showed initial interpretation overlook an early infarct in 11% of patients
Unenhanced CT does not show the arterial occlusion itself, except in the nonsensitivie HMCA sign), and does not show extent of distrubed cerebral perfusion, determined by site of occlusion, collateral blood supply, and inctracranial perfusion pressure. It does not allow the ;eptomeningeal collaterals to be seen.
Therefore – it is incapable of showing the volume of viable tissue at risk from low perfusion, which is the traget of thrombolytic treatment
Can CECT with CTA show the site of arterial occlusion, estimate leptomeningeal collateraliztaion, and determine the extent of severe parenchyumal perfusion deficit
Subarachnoid Bleed
(aneurysmal rupture)
Parenchymal Hematoma
(e.g. hypertensive bleed)
Courtesy of Stuart Pomerantz, M.D.

18. Hemorrhagic conversion of ischemic stroke
Important complication of AIS and treatment
Occurs in the ischemic bed

19. Is there a vessel occlusion?

20. CT Angiography
Important tool for rapidly and accurately assessing location of vessel occlusion
Is there a lesion amenable to interventional stroke therapy?
Prognostic implications: ICA-T vs. M1 vs. M2
May provide added value to the evaluation of the brain parenchyma
More sensitive assessment of the brain parenchyma

21. Neuro-CTA is our study of choice for all Emergent Neurovascular Indications
Intracranial Vasculature
Acute ischemic stroke
Intracranial stenosis
Aneurysms
AVMs
Venous Thrombosis
Courtesy of Stuart Pomerantz, M.D.

22. Neuro-CTA is our study of choice for all Emergent Neurovascular Indications
Extracranial Vasculature
Carotid artery stenosis/occlusion
Carotid/Vertebral dissection
Trauma
Courtesy of Stuart Pomerantz, M.D.

23. Neuro-CTA: Why? Accurate Fast Widespread availability of scanners
Not prone to artifactual signal dropout like MRI
Non-invasive
High-resolution
Preservation of bone detail
Depicts large and medium-sized vessels
Courtesy of Stuart Pomerantz, M.D.

24. MRA (3D TOF) performs reasonably well
CTA is highly accurate
Sensitivity 98.4%, Specificity 98.1% vs DSA
(Lev MH et al, JCAT 2001)
High inter-observer reliability
MRA (3D TOF) performs reasonably well
Sensitivity 84-87%, Specificity 85-98% vs DSA
Moderate inter-observer reliability
Less accurate for more distal occlusions
MIPs helpful: 3cm x 5mm increments, 3 orthogonal planes – especially helpful for the distal M2 branches

25. How much tissue is dead? And how much is at risk?

26. The Ischemic Penumbra Courtesy of Dr. Gil González
R.G. Gonzalez. Imaging-Guided Acute Ischemic Stroke Therapy: From “Time is Brain” to “Physiology is Brain” AJNR 2006; 27(4):
Courtesy of Dr. Gil González

27. PWI/DWI Mismatch the imaging surrogate of the penumbra
MRN
Infarct Core = DWI hyperintense lesion
Penumbra = hypoperfused tissue not in the core (e.g., MTT or TTP prolongation)

28. Selection for IAT
PWI/DWI mismatch is not discriminatory in the setting of large vessel occlusion – volume of MCA territory is ~300cm3
In our opinion, the more important question: How much is dead on arrival?
This is best assessed on DWI lesion
Sanak et al. Neuroradiology. 2006;48:

29. Importance of Infarct Volume
Final infarct volume is the best predictor of clinical outcome.

30. Stroke 2003; 34:
36 pts with acute MCA M1 occlusions imaged with XeCT within 6 hrs of onset: median NIHSSS 18,
26 treated: 3 IVT, 12 IAT, 11 bridging – subanalysis suggested that these findings also held for patients who reperfused (underpowered)

31. Selection for IAT
PWI/DWI mismatch is not discriminatory in the setting of large vessel occlusion – volume of MCA territory is 300cm3
The more important question: What is dead on arrival?  DWI lesion
An acute infarct volume threshold of 70cm3 has a high specificity for predicting a poor outcome (Sanak et al. 2006)
Sanak et al. Neuroradiology. 2006;48:

32. Acute Infarct Volume Threshold
Acute strokes imaged within 9hrs, n=54 pts

33. Various measures of the core infarct
MRI DWI (best estimate)
NCCT
CTA source images
CT perfusion

34. MRI DWI Considered the gold standard for depicting the infarct core
Identifies restricted diffusivity of water, which is thought to be related to energy failure  cytotoxic edema
Highly sensitive (91-100%) and specific (86-100%) within the first 6 hrs of stroke onset
Similar accuracy to 11C flumazenil PET, a reliable marker of neuronal integrity

35. Interpreting DWI DWI ⍺ e-1/T2 * e-ADC
Therefore, may get false positives from “T2 shine-through”
Must interpret with the ADC map

36. NCCT detection of acute infarction
0-3 hrs: cytotoxic edema – not much change in overall tissue water content
> 3-6 hrs: vasogenic edema
Δ HU ⍺ (degree of edema)
For every 1% ↑ in tissue H2O, X-ray attenuation ↓ by 3-5% (or ~2.5 HU)

37. NCCT signs of acute ischemia
Loss of gray-white matter differentiation:
“Insular ribbon”
Basal ganglia
Cortex
Basal
ganglia
Insular
ribbon
Cortex
MRN

38. Using narrow window and level settings (8HU W, 32HU L) can accentuate the small differences in attenuation due to ischemia
Sensitivity increases from 57% to 71%
Specificity 100%
Radiology 1999; 213:

39. Improved NCCT detection
MRN
Standard
Optimal

40. CT I-: Non-thrombolysis candidate
3 hours
Importance of narrow windows
Courtesy of Stuart Pomerantz, M.D.
24 hours
2 weeks

41. NCCT has poor sensitivity
CT is much less sensitive than MRI for detection of acute infarction (75% sensitivity1)
Has comparable specificity (>90%)
Barber et al. Stroke. 1999;30: Lansberg et al. Neurology. 2000;54:
1Barber PA, et al. Stroke. 1999; 30:
2Lansberg MG, et al. Neurology. 2000; 54:

42. MRI superior to CT for acute ischemic stroke
MRI=CT for acute hemorrhagic stroke
Chalela JA, et al. Lancet. 2007; 369:

43. NCCT vs DWI
Δ15 min.
MRN ; performed min apart

44. CTA source images Parenchymal evaluation performed on CT angiography
Hypodensity is related to decreased tissue constrast
Under steady state conditions, the hypodense lesion approximates the CBV (Hamberg et al, AJNR 1996)
Images viewed on narrow windows (W:30HU, L:30HU)

45. CTA source images
MGH
85yo F with DM, HTN presents with left hemiparesis, NIHSS 16 at 1h: 26 min after onset  IV tPA.

46. CTA-SI ≈ DWI Schramm et al. (Stroke 2002; 33:2426-2432):
20 AIS pts underwent CTA and DWI within 6hrs of onset (interval, 0.55± 0.25 hrs)
16/20 had vessel occlusion
CTA-SI lesion volume significantly correlated with DWI lesion volume (r=0.922, p<0.0001)
This is a complex problem and “improvements” in image acquisition raise ?s about the utility of this technique broadly

47. Dynamic perfusion imaging
Requires IV contrast injected at high rate
Images are rapidly acquired from a slab of tissue to monitor the first pass transit of the contrast bolus
Post-processing of the images (usually deconvolution with an arterial input function) produces maps of tissue-level perfusion: CBV, CBF and MTT
For CT perfusion, region of CBV depression estimates the infarct core

48. Core-Penumbra Mismatch
CBV
Cerebral Blood Volume
MTT
Mean Transit Time
CBF
Cerebral Blood Flow
Small defect in insula
Entire Inf. division MCA Territory Abnormal
Infarct Core:
CBV
likely to infarct despite Tx
Core
Penumbra
Mismatch
Penumbra:
MTT & CBF
At Risk
Salvageable

49. Successful Thrombolysis: Infarct Limited Mostly to Ischemic Core (CBV)
CBF
MTT
Mismatch
Majority of penumbra salvaged
Penumbra
Core
DWI
Courtesy of Stuart Pomerantz, M.D.

50. Conclusion: “Part 3” and “3 part series”
Advanced neurovascular imaging allows for dramatic improvement in the triage of stroke
This is a work in progress but absolutely critical
Understanding the power of that imaging and coupling it to the treatment advances allows for best possible treatments at any given time.
Device development for endovascular Rx continues to push forward
Taken together, these are powerful trends for the continued improvement in our ability to Rx acute ischemic stroke!