Background and Purpose
The concept of penumbra is based on animal experiments in which potentially reversible functional disturbances can be observed when blood flow decreases beyond a critical threshold. With reperfusion within a limited time window, these functional disturbances are reversible without leading to morphological damage and irreversible neurological deficits. In the last 20 years, surrogate markers of penumbra and irreversible tissue damage were studied, especially in regard to patients who could benefit from treatment in acute ischemic stroke. Positron emission tomography (PET) has been the gold standard but was replaced by diffusion- (DWI) and perfusion-weighted imaging (PWI) because of its wider distribution and the less complex logistics involved. There are some limitations with conventional DWI/PWI: increased diffusion signals can be reversible, and the determination of the threshold of critical perfusion by PWI is still a matter of ongoing debate.
Methods
Comparative studies with PET and MRI were performed in 3 groups of patients:
In 12 acute stroke patients, results from DWI (median, 6. 5 hours after symptom onset) and 11C-flumazenil (FMZ) PET (median, 85 minutes between DWI and PET) were compared with infarct extension 24 to 48 hours later on T2-weighted MRI. In 11 acute stroke patients, results from PWI (median, 8 hours after symptom onset) were compared with cerebral blood flow measurements obtained with [15O]H2O PET (interval, 60 minutes between PWI and PET). In 13 patients with acute (n = 6) or chronic stroke (n = 7), results from PWI/DWI were compared with PET of cerebral blood flow and oxygen consumption to detect mismatch or increased oxygen extraction fraction as surrogate markers of penumbra.
Results
From regions with increased DWI intensity, decreased apparent diffusion coefficient (ADC) and decreased FMZ binding probability curves were computed for eventual infarction, and 95% prediction limits were determined. These limits predicted 83.5% (FMZ), 84.7% (DWI), and 70.9% /ADC) of the final infarct volume. However, the false-positive predictions were much higher for the DWI variables (5.1 and 3.6 cm3 for DWI and ADC versus a median of 0 for FMZ). The comparison of volumes generated by different time to peak (TTP) thresholds (PWI) and hypoperfusion <20 ml/100 g per minute (PET) indicates that a TTP delay of 4 to 6 seconds yields a fair estimate of hypoperfusion. The PWI/DWI mismatch with TTP >4 seconds did not reliably correspond to the penumbra as assessed by PET (oxygen extraction fraction >150%). Only 8 of 13 patients with a mismatch had areas of penumbra.
In these cases, the penumbra volume was overestimated by MRI.
Conclusion
DWI correlates with FMZ results and, with a few exceptions, yields a good estimate of acute tissue damage and final infarct volume. PWI measures seem to be less reliable; the TTP prolongation of >4 seconds assessed only 83% of the volume of hypoperfusion <20 ml/100 g per minute. The mismatch volume imprecisely depicts increased oxygen extraction fraction, and, despite its clinical role for selection of patients for eventual therapy, it does not seem to be a reliable correlate of penumbra.