The occlusion of the terminal ICA and/or proximal MCA accounts for the majority of deaths and poor outcomes in patients with acute ischemic stroke
[13, 14]. Outcomes may be improved by treatment, but it is important to identify those who are most likely to benefit. In recent years it has been hypothesized that such patients may be identified using physiological information provided by imaging, specifically patients with a major diffusion/perfusion mismatch
[10, 11]. We have found in retrospective and prospective investigations that every acute stroke patient with terminal ICA and/or proximal MCA occlusion had a major (>100%) diffusion/perfusion mismatch when the DWI lesion was 70 ml or less. If verified, our findings suggest a simple alternative to perfusion imaging based solely on vessel imaging and diffusion MRI to identify those patients with major anterior circulation strokes that are most likely to benefit from treatment.
The use of advanced neuroimaging to identify patients most likely to benefit from therapy has been increasing in recent years. Diffusion MRI is used to estimate the core infarct, and perfusion-weighted imaging is used to delineate hypoperfused tissue. The diffusion/perfusion mismatch is considered the operational penumbra. This approach has been successfully used in treating patients with IV tPA (Tissue plasminogen activator) outside the 3 hour limit
. In the DEFUSE Trial
, it was shown that the use of tPA after 3 hours was effective if there was a significant diffusion/perfusion mismatch that included a DWI lesion of less than 100 ml. It has also been used as inclusion criteria in successful phase 2 trials of desmoteplase, DIAS and DEDAS
[10, 11], in which patients were given the drug outside the 3 hour limit.
However, recent data including a meta-analysis of the mismatch trials have raised questions regarding the effectiveness of the mismatch approach
[2, 16]. In parallel, there has been increasing concern over the reliability of perfusion imaging data
. Quantification of cerebral hemodynamics is affected by numerous factors which have not been standardized, including image acquisition, post-processing and choice of perfusion parameter
[4–6]. Furthermore, one of the usual measures used, the percentage of mismatch, ignores the volume. A 5 ml infarct and a 10 ml region of underperfusion would yield the same percentage of mismatch as a 50 ml infarct and a 100 ml region of underperfusion. Additional problems with perfusion methods include the time required for data acquisition and processing, and the risks related to further contrast administration. Most current approaches for post-processing of the perfusion data require its transfer to a dedicated workstation for further analysis, and a trained individual to process it.
Our observation that a proximal anterior circulation artery occlusion with a DWI lesion of 70 ml or less predicts a diffusion/perfusion mismatch of at least 100% suggests a simple alternative to perfusion methods for identifying major stroke patients most likely to benefit from treatment. This observation is logical considering the relevant physiology. Occlusion of the distal ICA and/or the proximal MCA puts at risk a large brain region that measures well over 200 ml
. The state of the brain at the time of evaluation depends on the vigour of the collateral flow, which determines the sizes of the infarct core and penumbra reflected in the diffusion/perfusion mismatch. The collateral flow that arises after ICA/MCA occlusion makes the core and penumbra interdependent parameters
[19, 20]. Excellent collateral flow accompanying a major occlusion will result in a small diffusion abnormality and a large mismatch (Figure
1), with the opposite result in the setting of poor collateral flow (Figure
We are not advocating a 100% mismatch for clinical decisions, only that in this subset of patients a large mismatch (definitely >20% and usually much larger) is almost certainly present and clinicians can reliably use this information to manage patients.
Our choice of the diffusion abnormality volume threshold of 70 ml was based on previous observations that patients with anterior circulation occlusions and diffusion abnormalities larger than 70 ml have poor outcomes regardless of treatment
[21–24], including successful endovascular recanalization
. Patients with small diffusion abnormalities had good outcomes only if the occluded arteries were promptly recanalized
. There may be a more optimal DWI threshold, and this is an area that merits further study. The measurement of the abnormal DWI volume can be performed manually or semi-automatically using a variety of software. Alternatively, it has been demonstrated that DWI or PWI lesion volumes can be reliably approximated using the formula ABC/2, where A, B, and C are the longest 3 orthogonal distances of the lesion as measured on the MR console or PACS workstation
It should be emphasized that the method proposed here is restricted to the specific condition of patients with distal ICA and/or mainstem MCA occlusions. Perfusion imaging may remain beneficial and superior in situations where there are occlusions of anterior circulation branch arteries, proximal ICA, and posterior circulation strokes. It is also probable that perfusion imaging will be of benefit in those without an identifiable occlusion, and in many situations in which a TIA is in the differential diagnosis.