In 1985, a prospective international cooperative study of extracranial to intracranial (EC-IC) bypass reported results for 1377 patients.1 Nonfatal and fatal stroke occurred both more frequently and earlier in the patients who had surgery.1 This trial failed for all of the subgroups due to an inability to identify a subgroup of patients with hypoperfusion as the primary and underlying cause of their stroke.
99Technetium single-photon emission computed tomography (Tc99 SPECT) scans with acetazolamide challenge have been used to evaluate EC-IC bypass surgery.2,3 Jeffree and Stoodley evaluated 19 patients, 88% of whom showed improvement in cerebral perfusion after EC-IC bypass surgery.2 Schmiedek et al evaluated 28 patients who suffered from hemodynamic cerebral ischemia with significant impairment of cerebrovascular reserve capacity.3 All patients who received follow-up Tc99 SPECT (26 patients) showed a significant improvement in cerebrovascular reserve capacity after surgery.
Computed tomography perfusion (CTP) studies using intravenous bolus administration of iodine-containing contrast media have recently become widely available to identify patients with acute stroke who may benefit from thrombolysis by discriminating potentially salvageable penumbra from irreversible ischemia.4–7 CTP has also been used in evaluating patients who received EC-IC bypass surgery, and revealed improved cerebral hemodynamics with a return to nearly normal perfusion in 10 patients who received a patent bypass.8
In this study, we investigated the effect of EC-IC anastomosis by automatic identification of mean transit time (MTT) prolongation and quantitative measurement of the brain area with MTT prolongation in CTP studies.
Fourteen patients who underwent both pre- and postoperative CTP studies before and after EC-IC bypass surgery from 2007 to 2010 were included in this investigation (Table 1). Indications for EC-IC bypass surgery in these cases were as follows:
- High-grade stenosis of the distal internal carotid artery (ICA) and occlusion at M1 in Patient 1, high-grade stenosis at the distal ICA in Patient 4, occlusion at M1 in Patient 3, and occlusion of the ICA in the other 11 cases. Causes of arterial stenosis or occlusion were Moyamoya disease in Patient 1, Moyamoya syndrome in Patient 13, and atherosclerotic disease in the other 12 cases.
- Clinical presentation of transient ischemic attack (TIA) was noted in eight cases and minor stroke in five cases. There was one case of pituitary adenoma with no TIA or stroke; bypass surgery was for preparation for a pituitary operation. Magnetic resonance (MR) imaging in three patients with clinical presentation of TIA showed a small acute infarct (Table 1).
- All these patients had evidence of hypoperfusion as evidenced by prolongation of MTT on the side with arterial occlusion or stenosis.
This was a retrospective study; all patients who received an EC-IC bypass performed from 2007 to 2010 with pre- and postoperative CTP studies were included. No EC-IC bypass patients in whom pre- and postoperative CTP studies were successfully performed were excluded. If a patient had two or more CTP studies after bypass surgery, only the first postoperative study was included in statistical analysis of volume changes for the area with MTT prolongation.
Our institutional review board approved the study. Written informed consent was obtained from each patient for the CTP study. The time interval from preoperative CTP to EC-IC bypass was 11 ± 9 days (range 1–34) (Table 1). The time interval from bypass surgery to postoperative CTP was 7 ± 4 days (range 2–13) (Table 2). Clinical follow-up was performed by telephone call, review of medical records, and review of imaging studies to check if any new stroke had occurred after the bypass surgery.
CTP examinations were performed using a spiral multidetector CT scanner (Brilliance 40, Philips Medical Systems, Cleveland, OH, USA). Non-ionic contrast media (40 mL of iohexol, Omnipaque, 350 mg/mL iodine) was administered at a rate of 4 mL/second via an intravenous cannula in the large vein in the forearm near the elbow on the right hand, followed by the same amount of normal saline.
CTP studies were performed at 80 kVp and 150 mA with a temporal resolution of 1 second. A brain area of 4 cm was examined in eight 5-mm slices. The temporal resolution was 1 second. Each patient was examined for 40 seconds. The angle of the slice was parallel to the frontal base of the skull. CTP covered the middle part of the brain between the frontal base and the cranial vault to encompass the anterior, middle, and posterior cerebral arterial territories.
CTP source data were transferred to a Philips CT workstation (Version 184.108.40.2064, Philips Medical Systems, Eindhoven, The Netherlands) for post-processing. The artery on the contralateral side of either the M2 or A2 with the shortest time to peak (TTP) was selected as the arterial input function. The venous output function was positioned at the lower straight sinus or the sinus confluence. After parametric maps were processed, we used Philips CT workstation software to identify brain regions with MTT prolongation and to calculate the area of the brain with abnormal MTT (Fig. 1).
The brain volume that showed impaired cerebral perfusion with MTT prolongation in preoperative CTP was 81 ± 46 cm3 (range 16.9–189). This decreased to 56 ± 43 cm3 (range 6–159) in postoperative CTP performed within 2 weeks (Table 2). Postoperative brain perfusion was improved and the EC-IC anastomosis was patent in 13 patients. One patient (Patient 6, Tables 1 and 2) who showed worse cerebral perfusion had an acute stroke during the bypass surgery. The EC-IC anastomosis was not patent in this patient. In the other 13 patients who had improved cerebral perfusion after bypass surgery, the average brain volume with a prolonged MTT was reduced by 32.3 ± 19.9 cm3 (range 7.1–65.8), representing an improvement of 42 ± 21% (range 11–77%) in perfusion within 2 weeks of surgery (Table 2).
No new onset of infarct or TIA was found in any patients during a follow-up period of 41 ± 16 months (range 14–60) after surgery. Follow-up was performed by telephone call for 12 patients and by reviewing medical and imaging records for the other two patients. For one patient (Patient 1), two postoperative CTP studies were performed. The later study (Case 1b in Table 2) showed a further reduction in brain volume with MTT prolongation.
Absolute quantification of CTP using venous output has been successfully validated by PET in normal volunteers.9–11 In addition to MTT, CTP can provide information about cerebral blood volume (CBV), cerebral blood flow (CBF), and TTP. Before stroke occurs, a brain with insufficient cerebral perfusion as a result of proximal arterial stenosis or occlusion usually has CBV elevation, CBF reduction, MTT prolongation, and TTP prolongation. The present study evaluated changes in brain volume with MTT prolongation and not volume changes for CBV, CBV, or TTP because the software available provides automatic identification and measurement of brain area with a prolonged MTT, but not areas with CBV elevation, CBF reduction, and TTP prolongation. With currently available technology, identification of abnormal brain area with CBV elevation, CBF reduction, or TTP prolongation requires visual identification of these regions, visual comparison with the surrounding tissue or the contralateral hemisphere, and manual drawing of the region of interest.12 The measurement variability (precision) of CTP is low (15–30%) when techniques based on visual interpretation and manual drawing of the region of interest (ROI) are used.4 The current software provides automatic identification and area measurement of the abnormal brain area with prolonged MTT. Use of this automatic quantitative measurement removed interobserver variability for visual identification of the area with prolonged MTT and manual drawing of the ROI.
One drawback of CTP studies is the presence of ionizing radiation. We used a low-radiation technique, which demonstrated an acceptable level of data quality: 80 kVp, 150 mA, a temporal resolution of 1 second, and a relatively short data collection time of 40 seconds. The equivalent dose used for the brain in one CTP was approximately 1.77 mSv, which is similar to the dose used for one non-contrast CT of the brain (∼1.89 mSv). None of our patients presented any focal radiation symptoms such as hair loss, skin itching, or skin redness. Because of the presence of ionizing radiation, sequential follow-up of cerebral perfusion after EC-IC bypass was not requested clinically.
MR perfusion has benefits of no ionization radiation and a lower frequency of contrast-induced adverse reactions compared to CTP. MR perfusion provides relative data at present. Absolute quantification of MR perfusion using venous output function often overestimates CBF.13–15 In addition, no reliable automatic demonstration and measurement of brain area with abnormal perfusion available yet. Therefore, it is difficult to evaluate brain volume of abnormal perfusion on MR perfusion at present.
This study evaluated early CTP changes in the 2 weeks after EC-IC bypass surgery. The anastomosis takes some time to enlarge after EC-IC bypass. Therefore, a longer follow-up time might reveal greater improvements in brain perfusion, as observed for Patient 1.
A recent randomized trial (the Carotid Occlusion Surgery Study, COSS) found very high 30-day rates for ipsilateral ischemic stroke (14.4%) in an EC-IC surgery group compared to 2% in a nonsurgical group.16 In our study, we had a lower stroke rate (7%), with just one stroke during surgery. For EC-IC bypass surgery to be useful in stroke prevention, it is important to reduce perioperative complications in the 30 days after surgery. In addition to a good bypass technique, this may be achieved by quality control of anesthesia, blood pressure control, and medical and nursing care during and after the operation.
Because of limitations in the CT scanner available, CTP in this study could not cover the whole brain. The extent of the brain encompassed from the caudal to the cephalic regions was 4 cm. Some brain outside of the 4-cm perfusion coverage may also have benefitted from the bypass surgery. The relatively small number of cases assessed in this study is a further limitation. A future, larger-scale study using automatic quantitative measurement of whole-brain CTP or MR perfusion studies may facilitate our understanding of the value of EC-IC bypass surgery.
In conclusion, follow-up in patients with CTP within 2 weeks after surgery helps in understanding future patient outcome. This study demonstrated a positive correlation between improvement in brain perfusion shown on MTT, EC-IC bypass patency, and patient outcome.
This study was supported by a research grant from Taipei Veterans General Hospital (grant number V98C1-108).
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