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Gillian Lieberman, MD
Imaging ischemic strokes:Imaging ischemic strokes:Correlating radiologicalCorrelating radiological
findings with thefindings with the
pathophysiologicalpathophysiological evolutionevolutionof an infarctof an infarctJayJayChyungChyung, PhD, HMS III, PhD, HMS III
Gillian Lieberman, MDGillian Lieberman, MD
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Jay Chyung Phd, HMS III
Gillian Lieberman, MD
Patient A: historyPatient A: history91 y.o. woman
Acute onset R sided weakness
and aphasia
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Jay Chyung Phd, HMS III
Gillian Lieberman, MD
DDxDDxStroke (Ischemic ~80% or Hemorrhagic ~20%)
Transient ischemic attack (TIA)
Seizure with post-ictal
paralysis
Intracranial tumor (with secondary hemorrhage,
seizure, or hydrocephalus)
Migraine
Metabolic encephalopathy
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Jay Chyung Phd, HMS III
Gillian Lieberman, MD
Acute Stroke ManagementAcute Stroke ManagementNon-contrast head CT
Quickly identifies hemorrhagic strokes (fresh blood is
bright on CT)Ischemic stroke
Can administer tPA within 3hrs (systemic) or 6 hrs (intra- arterial)Identify source of ischemicstroke: Embolic, Thrombotic,
Low-flow
Prevent secondary damageand expansion of infarct
Hemorrhagic stroke
DO NOT administer tPAMildly reduce blood pressure
Administer products toreduce interstitial fluid levels
(eg. Mannitol)
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Jay Chyung Phd, HMS III
Gillian Lieberman, MD
Patient A: NonPatient A: Non--contrast CTcontrast CTFindings*** No evidence of
hemorrhage***
Loss of gray-white matterdistinction in L MCA
territory
Sulcal
effacement
Slight mass effect on L lateralventricle
No midline shift
PACS, BIDMC
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Jay Chyung Phd, HMS III
Gillian Lieberman, MD
Patient A: Progression of InfarctPatient A: Progression of InfarctFindings
No evidence ofhemorrhagic
transformation
Hypodensity in region ofL MCA infarctMass effect on L lateralventricle with midline
shift
PACS, BIDMC
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Jay Chyung Phd, HMS III
Gillian Lieberman, MD
Mechanisms of ischemic stroke injuryMechanisms of ischemic stroke injuryEvent in Neurons TimeLoss of blood supply
0
O2
depletion 10 sec
Glucose depletion
2-4 min
Conversion to anaerobic respiration 2-4 minExhaustion of cellular ATP 4-5 minNEURONS have very limited stores of energy in the forms of
phosphocreatine and glycogen. In contrast, GLIAL cells havegreater energy reserves and are less energy demanding.
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Jay Chyung Phd, HMS III
Gillian Lieberman, MD
Mechanisms of ischemic stroke injuryMechanisms of ischemic stroke injury
ATP depletion
Na+
-K+
ATPase dysfunctionLoss of electrochemical gradient: Anoxic depolarization
Ca++
influx
Phospholipase and protease activationNecrosis
Apoptosis pathway
Edema, FAS death ligands, cytokine release, free radical generation, acidosis
Massive glutamate release
Mitochondrial
dysfunction
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Jay Chyung Phd, HMS III
Gillian Lieberman, MD
Early CT changes from intracranialEarly CT changes from intracranial
edemaedema
Loss of blood supply
Cell death
ATP depletion
EDEMA
Edema: 0-20 HU; Gray matter: ~46 HU; White matter: ~40 HU
1.
Effacement of gray-white matter distinction asedema reduces the small difference in gray and
white matter attenuations
2. Effacement of sulci due to swelling withinlimited space3.
Mass effect on ventricles due to swelling within
limited space
* Earliest CT changes seen several hours to daysafter initial loss of blood supply depending on
size of infarct and volume of edema.
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Jay Chyung Phd, HMS III
Gillian Lieberman, MD
Progression of an ischemic infarctProgression of an ischemic infarctLoss of blood supply
Cell death
ATP depletion
EDEMA
CYTOKINES
FAS DEATH
LIGANDS
FREE RADICAL
DAMAGE
ACIDOSIS
Increase in infarct size over time is possible
Ischemic Penumbra
-
the region surrounding the
infarcted tissue is subjected to numerous stresses: Decreased perfusion Abnormal cerebrovascular pressureautoregulation Compression by neighboring edema
Active inflammation
Free radical damage from infarcted
region and
neutrophils, astrocytes, microglia Induction of apoptosis by FAS death ligands
CELL DEATH
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Jay Chyung Phd, HMS III
Gillian Lieberman, MD
Pt B: Progression of an ischemic infarctPt B: Progression of an ischemic infarct
Time = 3.25 hr
30 hr
8 days
Late CT changes:
Increased infarction area, mass effect on ventricle, loss of sulci,
hypodensity
in infarcted
tissue
* Hypodensity
due to replacement of tissue by fluid
[Figure from Pantano et al. 1999. Stroke 30:502-507]
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Jay Chyung Phd, HMS III
Gillian Lieberman, MD
Hemorrhagic transformation ofHemorrhagic transformation of
ischemic strokeischemic strokeHemorrhagic transformation of ischemic stroke results from
reperfusion injury.
Reperfusion injury:
Restoration of blood flow through a
previously occluded intracranial vessel that results in vessel walldestruction and hemorrhage.
Spontaneous or tPA-induced clot lysis
O2
combines with toxic metabolites to generate superoxide O2-
Invading neutrophils
convert O2
to O2
-
Blood-brain barrier destruction from free radical damage to
endothelial cells AND ischemic endothelial cell death (3-4 hrs)
Loss of blood supply
Cell death
ATP depletion
FREE RADICAL
DAMAGE:
METABOLIC
BYPRODUCTS
NEUTROPHILS
O2
HEMORRHAGE
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Jay Chyung Phd, HMS III
Gillian Lieberman, MD
Patient C: HemorrhagicPatient C: Hemorrhagic
transformation of an ischemic stroketransformation of an ischemic stroke
[Figure from http://www.strokecenter.org/education/ais_pathogenesis/16_hemorrhagic_conversion.htm]
J Ch Phd HMS III
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Jay Chyung Phd, HMS III
Gillian Lieberman, MD
tPAtPA--induced hemorrhagicinduced hemorrhagic
transformation: potential treatmenttransformation: potential treatment1.
tPA
treatment for ischemic stoke often leads to secondary
hemorrhagic transformation due to reperfusion injury
2.
Current models state that reperfusion injury occurs in large part
from free radical damage following clot-lysis
3.
Therefore, delivery of tPA
WITH
anti-oxidants should reduce the
probability of hemorrhagic transformations
Animals models support co-administration of tPA
with anti-oxidants
in the prevention of secondary hemorrhagic transformation
Lapchak
and Zivin. 2003. STROKE 34(8):2013-8
Lapchak et al. 2001. STROKE 32(1):147-153
J Ch Phd HMS III
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Jay Chyung Phd, HMS III
Gillian Lieberman, MD
Ischemic strokes: imaging with MRIIschemic strokes: imaging with MRI
DiffusionDiffusion--Weighted Imaging (DWI)Weighted Imaging (DWI)
DWI signal intensity is related to the apparentdiffusion coefficient (ADC) of watermolecules (independent of the amount of
water)
ADC(water) decreases by ~50% within 5-10min of ischemic stroke due to intracellularedema and also possibly decreased
temperature
recall that ATP is depleted from
neurons within 4-5 min.
*** DWI changes can be seen within minutes
of an ischemic stroke.
Loss of blood supply
Massive depolarization
ATP depletion
intracellular ions
INTRACELLULAR
EDEMA
Cell death
EXTRACELLULAR
EDEMA
J Ch Phd HMS III
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Jay Chyung Phd, HMS III
Gillian Lieberman, MD
Pt D: Imaging ischemic strokes withPt D: Imaging ischemic strokes with
MRI DiffusionMRI Diffusion--Weighted Imaging (DWI)Weighted Imaging (DWI)
PACS, BIDMC
Left inferior
temperal/occipital
lobe ischemic infarct
J Ch Phd HMS III
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Jay Chyung Phd, HMS III
Gillian Lieberman, MD
Summary slideSummary slideLoss of bloodsupply
Cell Death
ATP depletion
Edema, cytokine release,
free radical damage, FAS
death ligands
Reperfusion injury
Hemorrhagictransformation
Cell Death
DWI:
increased signal intensity(5-10 min post-ischemic injury)
Early CT changes:GW & sulcal
effacement,
mass effect (hrs to days)
Bright lesionon CT
Late CT changes:Hypodensity, mass effect,
possibly enlarged infarct
region
Jay Chyung Phd HMS III
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Jay Chyung Phd, HMS III
Gillian Lieberman, MD
ReferencesReferencesEaston JB et al. Cerebrovascular
diseases,
Chapter 366 in Harrisons Principles of Internal Medicine
1998, 14th
Edition: 2325-2348.
Ishikawa M et al. Platelet-leukocyte-endothelial cell interactions after middle cerebral artery occlusion andreperfusion.
J Cereb
Blood Flow Metab. (2004) 24(8):907-15.
Lapchak
PA et al. Pharmacological effects of the spin trap agents N-t-butyl-phenylnitrone
(PBN) and 2,2,6, 6-
tetramethylpiperidine-N-oxyl (TEMPO) in a rabbit thromboembolic
stroke model: combination studies with the
thrombolytic tissue plasminogen
activator.
Stroke
(2001) 32(1):147-153.
Lapchak
PA and Zivin
JA. Ebselen, a seleno-organic antioxidant, is neuroprotective
after embolic strokes in rabbits:
synergism with low-dose tissue plasminogen
activator.
Stroke
(2003) 34(8):2013-8.
Onteniente
B et al. Molecular pathways in cerebral ischemia.
Mol Neurobiol.
(2001) 27(1):33-72.
Pantana
P et al. Delayed increase in infarct volume after cerebral ischemia: Correlations with thrombotic treatment
and clinical outcomes.
Stroke
(1998) 30:502-507.
Sen
S. Magnetic resonance imaging in acute stroke.
eMedicine: http://www.emedicine.com/neuro/topic431.htm
(2004).
Wang X and Lo EH. Triggers and mediators of hemorrhagic transformation in cerebral
ischemia.
Mol Neurobiol. (2003) 28(3):229-44.
Welch KMA et al. Magnetic resonance assessment of acute and chronic stroke.
Prog. in Cardiovasc. Dis.
(2000)43(2): 113-134.
http://www.strokecenter.org/education/ais_pathogenesis/16_hemorrhagic_conversion.htm
All websites as of 9/20/04
Jay Chyung Phd HMS III
http://www.emedicine.com/neuro/topic431.htmhttp://www.emedicine.com/neuro/topic431.htmhttp://www.strokecenter.org/education/ais_pathogenesis/16_hemorrhagic_conversion.htmhttp://www.strokecenter.org/education/ais_pathogenesis/16_hemorrhagic_conversion.htmhttp://www.strokecenter.org/education/ais_pathogenesis/16_hemorrhagic_conversion.htmhttp://www.emedicine.com/neuro/topic431.htm8/22/2019 AVC Radiologia
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Jay Chyung Phd, HMS III
Gillian Lieberman, MD
AcknowledgementsAcknowledgementsDan Cornfeld, MD
Larry Barbaras
Gillian Lieberman, MD
Pamela Lepkowski