Persistent Benign Oligemia Causes CT Perfusion Mismatch in Patients with Intracranial Large Artery Occlusive Disease during Subacute Stroke

CT perfusion (CTP) imaging provides quantitative parameters of cerebral perfusion using cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). It is increasingly being used in selecting patients for thrombolytic therapy 1, 2. Penumbra is usually characterized as the mismatch area with increased or normal CBV and prolonged MTT 3. MTT ratio (symptomatic ipsilateral MTT compared with the contralateral side), with a threshold more than 145%, affords the most accurate delineation of the tissue at risk of infarction 4. The recently published study 5 described the concept of benign oligemia at acute phase of stroke and distinguished it from penumbra. Intracranial large artery occlusive disease (ICAD) accounts for about one quarter to one-third of all stroke patients in Asians 6, 7. Little is known about the clinical significance of the mismatch shown on CTP in patients with ICAD during subacute stroke. Will the mismatch area be persistent? Is it a real penumbra? In the present study, consecutive stroke patients who were referred for CTP in the Prince of Wales Hospital, Hong Kong, in 2009 were screened. Inclusion criteria were as follows: (1) baseline CT angiography (CTA), CTP, and/or additional vascular imaging magnetic resonance angiography (MRA), (2) ICAD was diagnosed when CTA and MRA showed stenosis or occlusion of intracranial large artery, (3) with infarction in corresponding middle cerebral artery (MCA) territory in acute (within 1 day) and subacute group (more than 1 day) of ischemic stroke, and (4) more than 20% mismatch on CTP. Exclusion criteria were as follows: (1) bilateral intracranial occlusive stenosis, (2) unsatisfactory quality of CTP studies, (3) with document source of embolism from cardiac or extracranial artery, and (4) unclear clinical data. CT perfusion was performed on a multidetector scanner (GE Healthcare, Tokyo, Japan), as a 60-second cine series, beginning 5 seconds after a 50-mL injection of IOP300. Source images were transferred to a workstation and were evaluated with CT Perfusion 3 software (GE Healthcare). To obtain arterial input and venous output, we placed 3- to 5-pixel squared regions in unaffected large artery (such as anterior cerebral artery) and vein (such as superior sagittal sinus) respectively. Bilateral MCA territories were circled as region of interest. Any area of old infarct was excluded. spss 12.0 (SPSS Inc, Chicago, IL, USA) was performed for statistical analyses. In all analyses, nonparametric Mann–Whitney U-test was used for comparison of continuous variables, and chi-squared test was used for categorical variables. Values were considered significantly different with P < 0.05. Thirty-four stroke patients with ICAD and infarction in relevant MCA territory were screened. Four patients were excluded due to poor quality image or incomplete data, and ten patients were excluded due to less than 20% mismatch. Finally, fourteen patients were enrolled in subacute group and six in acute group. An example of mismatch area was shown in Figure 1. Table 1 demonstrated the characteristics of recruited patients and the value of CTP-related parameters. Due to small sample size, the patients in acute group were older and severer than those in subacute group. The median time between CTP and onset of symptom was 6 days (range, 3–30 days) in subacute group and 180 min in acute group. The values of CBF, CBV, and MTT were comparative between patients in acute and subacute stage. The value of CBV ratio was higher in patients in subacute group than in those in acute group (1.3 versus 1.0, P = 0.025). The MTT ratio in both groups was higher than 145%. This study was a small sample size study, which provided the very preliminary data about the blood perfusion in patients with ICAD. The findings indicated that CTP mismatch can be persistent in the subacute phase of stroke in patients with ICAD, showing similar values of CTP parameters with penumbra. Penumbra is thought to be the area, which will progress to infarction if not salvaged 1. Thus, the long-lasting mismatch shown in our present study should be overestimated benign oligemia rather than penumbra. Although the overestimated benign oligemia has been proved in acute phase of stroke 5, 8, it is still an ambiguous concept during subacute phase 3, 9. Our present study indicated the possibility of benign oligemia in subacute stage. Further study is needed to delineate the difference between oligemia and penumbra in patients with ICAD. In conclusion, our study demonstrated the existence of mismatch area with similar characters to penumbra in patients with ICAD during subacute phase of stroke. We suppose the mismatch area should be benign oligemia rather penumbra. In patients with ICAD, more attentions should be paid to interpretation of CTP mismatch, especially during the process of selecting candidate to receive thrombolytic treatment. The study was supported by the S.H. Ho Cardiovascular Disease and Stroke Center, Institute of Vascular Medicine, Chinese University of Hong Kong. Dr Li was supported by the Henry Leung Fellowship program, Department of Medicine & Therapeutics, Chinese University of Hong Kong. The authors declare no conflict of interest.