ISCHEMIC STROKE

Ischemic penumbra

Created 21/03/2021, last revision 13/04/2022

Concept of ischemic penumbra

  • the extent of brain damage during stroke depends on the severity and duration of the cerebral blood flow (CBF) disorder
  • there are two major zones of injury within the ischemic area: the core and the penumbra
  • when the blood flow decreases, at first, loss of function with intact structural integrity occurs (functional threshold)
  • with a further decrease in CBF or with increased duration of blood flow deficit, an irreversible failure of membrane functions and permanent morphological changes occur (morphological threshold) –
    • a decrease in regional flow < 55 ml / 100 g of tissue/minute leads to inhibition of proteosynthesis
    • < 35 ml – stimulation of anaerobic glycolysis
    • < 20 ml – loss of electrical function
    • < 10 – 12 ml – necrosis
  • neurons in the area with CBF below the morphological threshold (infarct core) represent the tissue that has already dead or may survive for only a very limited time
  • brain tissue with perfusion values ​​between the two thresholds (CBF 12-18 ml/100g/min) is called the ischemic penumbra” and may remain viable for several hours
  • cells in the penumbra eventually die if early reperfusion is not established; since collateral circulation can’t maintain the neuronal demand for oxygen and glucose indefinitely ⇒ penumbra shrinks during persistent artery occlusion  Final infarction on DWI is same as penumbra on initial CT perfusion in patient with persistent MCA occlusion
    • neurons of the hippocampus, basal ganglia, and some areas of the cortex are particularly susceptible
  • the rescue of neurons  in ​​ischemic penumbra is the primary target of recanalization therapy
Penumbra concept
Core Penumbra Normal tissue
CBF mL/100g/min
< 12
12-18
> 18
EEG
0
reduced
normal
SSEP
0
reduced
preserved
histology
infarction
normal
normal
membrane potential
0
0 (reversible)
loss on neuron function
normal
vitality
no
preserved
normal
Penumbra concept

Penumbra detection

CT perfusion (CTP)

  • CT perfusion (CTP) can help to differentiate irreversible ischemia (core) and ischemic penumbra (viable tissue with reduced perfusion) and benign oligemia
  • different software packages use different combinations of parameters to define the core and penumbra
  • a common definition for penumbra:
    • hypoperfused brain at risk of progression to infarction (salvageable)
    • ↑ T-max  >6 seconds,  or ↑ mean transit time (MTT) or time to peak (TTP) > 145% of the healthy hemisphere)
    • a moderate decreased cerebral blood flow (CBF),  >30% of contralateral side
    • normal / ↑ cerebral blood volume (CBV)  – due to autoregulation
  • a common definition for core:
    • infarcted brain, not salvageable
    • ↑ T-max  (TTP, MTT)
    • ↓↓ cerebral blood flow (CBF)  (<30% of normal, corresponds to DWI lesion on MRI)   CTP core area with CBF<30% corresponds to DWI lesion on MRI
    • ↓↓ cerebral blood volume (CBV)  (< 40% normal)
CBV
CBF
MTT
Ischemic core
↓↓
↓↓↓
(< 30%)
↑↑
Penumbra
N or ↑
↓↓
(> 30%)
↑↑
Benign oligemia
N or ↑
↑ or ↑↑
Chronic, compensated occlusion/stenosis
N
N
↑ or ↑↑
Penumbra concept
Penumbra on CTP with normal or increased CBV
Core on CTP

MR perfusion (PWI)

  • MR perfusion imaging (PWI) is performed by the “first-pass bolus” technique with intravenous administration of gadolinium
  • the same parameters can be obtained as in CT perfusion (CBV, CBF, MTT, TTP)
  • tissue with reduced perfusion (prolonged MTT) includes a complete infarction, a penumbra, and a region of benign oligemia
  • ischemic core correlates closely with restricted diffusion lesion (DWI lesion) apart from decreased CBF and CBV
  • the difference between the area of decreased perfusion and DWI lesion determines the size of the penumbra (PWI/DWI mismatch)
MR PWI-DWI mismatch
PWI-DWI mismatch - the difference between the area of decreased perfusion and DWI lesion determines the size of the penumbra (PWI/DWI mismatch)
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