Ischemic penumbra

David Goldemund M.D.
Updated on 17/03/2024, published on 20/06/2023

Concept of ischemic penumbra

  • the extent of brain damage during a stroke depends on the severity and duration of the cerebral blood flow (CBF) disorder → Regulation of cerebral blood flow
  • within the ischemic area, two major zones of injury are identified :
    • core 
    • penumbra
  • as blood flow decreases, an initial loss of function occurs while structural integrity remains intact (functional threshold)
  • with a further decrease in CBF or prolonged blood flow deficit, irreversible loss of membrane functions and permanent morphologic changes occur (morphologic threshold)
    • a decrease in regional flow to < 55 mL / 100g of tissue/minute leads to inhibition of proteosynthesis
    • < 35 mL – stimulation of anaerobic glycolysis begins
    • < 20 mL – loss of electrical function occurs
    • < 10 – 12 mL – necrosis
  • neurons in areas where CBF falls below the morphologic threshold (infarct core) represent tissue that is already dead or only viable for a very limited time
  • brain tissue with perfusion values ​​between the two thresholds (CBF 12-18 ml/100g/min) is termed the ischemic penumbra“; this tissue may remain viable for several hours
  • without early reperfusion, cells in the penumbra will eventually die, as collateral circulation cannot sustain the neuronal demand for oxygen and glucose indefinitely ⇒ penumbra shrinks with prolonged arterial occlusion  The final infarction on DWI corresponds to the penumbra on initial CT perfusion in patients with persistent MCA occlusion
    • neurons of the hippocampus, basal ganglia, and some cortical areas are particularly vulnerable
  • identifying and quantifying the penumbra can guide clinical decisions, as rescuing neurons in the ischemic penumbra is the primary objective of recanalization therapy
Penumbra concept
core penumbra normal tissue
CBF mL/100g/min
< 12
> 18
membrane potential
0 (reversible)
loss of neuron function
Penumbra concept

Penumbra detection

CT perfusion (CTP)

  • CT perfusion (CTP) can help differentiate between irreversible ischemia (core) and ischemic penumbra (viable tissue with reduced perfusion), as well as benign oligemia
  • software packages use various combinations of parameters to define core and penumbra
  • a common definition of penumbra:
    • hypoperfused brain at risk of progression to infarction, yet salvageable
    • increased T-max >6 seconds,  or mean transit time (MTT) or time to peak (TTP) > 145% of the healthy hemisphere   Core and penumbra on CT perfusion
    • moderate decrease of cerebral blood flow (CBF);  > 30% compared to the contralateral (normal) side
    • normal or ↑ cerebral blood volume (CBV)  – due to autoregulation
  • a common definition of core:
    • infarcted, unsalvageable tissue
    • ↑ T-max  (↑TTP, MTT)
    • ↓↓ CBF (< 30% of normal values); correspondïng to a DWI lesion on MRI)   CTP core area with CBF<30% corresponds to DWI lesion on MRI
    • ↓↓ CBV  (< 40% of normal)
ischemic core
(< 30%)
N or ↑
(> 30%)
benign oligemia
N or ↑
↑ or ↑↑
chronic, compensated occlusion/stenosis
↑ or ↑↑
Penumbra concept
Penumbra on CTP with normal or increased CBV
Core on CTP

MR perfusion (PWI)

  • MR perfusion imaging (PWI) uses the “first-pass bolus” technique, utilizing intravenous gadolinium
  • the same parameters as with CTP can be obtained (CBV, CBF, MTT, TTP)
  • tissue with reduced blood flow (indicated by a prolonged MTT) encompasses:
    • infarct (core)
    • penumbra
    • benign oligemia regions
  • the ischemic core closely correlates with restricted diffusion lesion (DWI lesion) and is characterized by decreased CBF and CBV
  • the difference between the tissue volume showing a perfusion deficit (on PWI) and the tissue volume already infarcted (on DWI) is termed the PWI/DWI mismatch
  • PWI/DWI mismatch represents the ischemic penumbra
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)


  • the ischemic penumbra refers to brain tissue that is hypoperfused due to an ischemic stroke but remains potentially salvageable if blood flow is restored promptly
  • penumbra is typically identified using imaging techniques such as CT perfusion or MRI diffusion and perfusion studies
  • these techniques help to differentiate the penumbra from the infarct core by showing areas of reduced blood flow that have not yet been irreversibly damaged
  • reperfusion therapies such as intravenous thrombolysis (using alteplase or tenecteplase) and mechanical thrombectomy (endovascular removal of the clot)
  • these treatments aim to restore blood flow to the penumbra as quickly as possible
  • the survival time of the ischemic penumbra can vary significantly among individuals, generally ranging from tens of minutes to several hours post-stroke
  • the exact duration depends on various factors, including the severity of the blood flow reduction and the presence of collateral blood vessels
  • it depends on how quickly reperfusion therapy is administered and reperfusion established
  • early and effective treatment increases the likelihood of saving most, if not all, of the penumbral tissue
  • if the ischemic penumbra is not treated promptly, it is likely to undergo irreversible damage and become part of the infarcted core

Related Content

You cannot copy content of this page

Send this to a friend
you may find this topic useful:

Ischemic penumbra