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
- 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
| 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 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)
- ↓↓ 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 ↑↑
|
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)
