Is STA really a low-flow graft? A quantitative ultrasonographic study of the flow of STA for cerebral revascularization in MMD patients

Objective: Direct revascularization


| INTRODUC TI ON
Moyamoya disease (MMD) is a unique chronic progressive cerebrovascular disease characterized by stenosis or occlusion of the bilateral arteries around the circle of Willis, accompanied by the formation of arterial collateral circulation. 1,2 The prevalence of MMD range from 0.35 to 0.94 per 100,000 populations, and its sex ratio (women to men) is 1.8. [3][4][5] The pathogenesis of MMD remains not clear. RNF213 is a susceptibility gene for MMD. 6,7 Patients with MMD show different clinical symptoms, such as a transient ischemic attack, ischemic and hemorrhagic stroke, and epilepsy. 8,9 Currently, a cure for MMD is not yet available. 2 Improvement in cerebral blood flow (CBF) may protect against stroke in the future. Strategies for the surgical treatment of patients with MMD remain controversial. Several experienced surgeons recommend a combination of direct and indirect approaches. 10 For adult patients with MMD, direct bypass is recommended as the first-line treatment strategy. The superficial temporal artery-middle cerebral artery (STA-MCA) bypass is the most commonly used procedure to restore blood flow (BF) in the ischemic brain. Traditionally, the STA was considered a low-flow bypass because the flow provided by the STA was thought to be approximately 10-20 mL/min. However, the STA can provide a more robust flow as a donor vessel. In Charbel's study, the cut flow of the STA ranged from 8 to 186 (median, 68) mL/min, and the bypass flows ranged from 1 to 154 (median, 48) mL/min. 11 In another clinical report with a small sample size, the postoperative STA graft flow measured using quantitative magnetic resonance angiography (MRA) showed a mean value of 79 mL/min. 12 However, the factors affecting STA graft flow remain unknown.
Several imaging examinations, including digital subtraction angiography (DSA), computed tomography angiography (CTA), and MRA, are used to detect whether a successful bypass treatment. [13][14][15] DSA remains the gold standard for its detection. 16 However, DSA is an invasive and costly technique. CTA and MRA can also be used for posttreatment evaluation. 17,18 However, CTA and MRA cannot detect CBF, flow rate, or blood supply range. Additionally, these two modalities are relatively costly.
Quantitative ultrasonography, a noninvasive inspection and costeffective method, can serve as an alternative tool to assess bypass patency. 19 Blood vessel diameter, b BF velocity (BFV), and pulsation index (PI) score can be determined using quantitative ultrasonography. Moreover, it can detect changes at any time point during the perioperative period. The results of direct revascularization can be easily assessed using quantitative ultrasonography.
In this study, we aimed to detect the BF of the blood supply artery after direct revascularization and analyze the factors that affect BF.

| Patient selection
Patients with MMD who underwent STA-MCA bypass surgery at Nanfang Hospital between January 2018 and January 2021 were enrolled in this study ( Figure 1). Quantitative ultrasonography was performed within 24 h before DSA in all patients with MMD. All the surgeries were performed by an experienced clinical neurosurgeon. This study was approved by the Institutional Review Board of Nanfang Hospital (NFEC-2022-442). All patients provided informed consent before inclusion in this study.

| Brief description of surgical procedure
All bypasses were performed by end-to-side anastomosis of the parietal branch of the STA (STA-PB) to the MCA (frontal and/or temporal M4 branches of the MCA). In brief, the 10-CM STA-PB was dissected. Craniotomy was then performed. After opening the dura, one branch of the MCA was selected as the recipient vessel and trapped using two temporary clips placed 1 cm apart. A longitudinal incision was made in the recipient vessel, which was irrigated with heparin solution. The stump of the donor vessel was shaved obliquely to fit the recipient's side. A total of 8-12 interrupted sutures were made, with 3-5 on each side. Indocyanine green video angiography (performed using a commercially available microscope, OPMI Pentero, Carl Zeiss Co, Oberkochen, Germany) was used to validate the patency of the anastomosis.

| Quantitative ultrasonography
Quantitative ultrasonography images were blindly and independently reviewed by two senior sonologists. The measurement method and precautions for quantitative ultrasonography were performed, as described previously. 19 In brief, the patients were F I G U R E 2 MBC Scale. M (M1 lumen: 0, normal; 1, stenosis; 2, occlusion). B (MCA bifurcation: 0, MCA bifurcation occlusion; 1, MCA bifurcation and communication between the blood vessels are normal). C (Cortical vascular integrity: 3, more than two-thirds of the MCA cortical arterial branches can be visualized on preoperative digital subtraction angiography; 2, one-third to approximately two-thirds can be visualized; 1, less than one-third can be visualized). 1, less than one-third can be visualized (Grade C). The total score of M + B + C ranged from 1 to 6 points. A higher score indicated a better MCA network, indicating that more blood could be received from the donor artery.

| Follow-up
Patients who underwent STA-MCA bypass surgery were followed up at least once in an outpatient clinic visit 6 months after the procedure and annually thereafter by telephone interviews or clinic visits.
Quantitative ultrasonography and modified Rankin Scale (mRS) score

| Statistical analyses
Continuous variables are reported with mean ± standard deviation and were compared among groups using two-way

| The results of all ultrasonography indices
The results of all ultrasonography indices over time (Pre, day 1, day 7, >6 months [long term]), including D, flow, PI, RI, and Vm are shown in Table 2 and Table S1. The vessels included the STA-PB and STA-FB on the bypass side, the STA-PB and STA-FB on the contralateral side, and the RA.

| Comparisons of all indices between the parietal branch of the superficial temporal artery (STA-PB) at the bypass side and radial artery
In paired comparisons, all STA-PB indices on the bypass side were significantly different from the corresponding RA indices postoperatively (all p < 0.05, Table 2). As shown in Figure 4, the flow was higher in the RA than in the STA-PB before bypass surgery (p < 0.001); however, after bypass surgery, the flow was significantly higher in the STA-PB than in the RA (all p < 0.05). The diameter, PI and RI were higher in the RA than in the STA-PB at any time points (all p < 0.05), however, the Vm were lower in the RA than in the STA-PB at any time points (all p < 0.01).  Table S1 and Table 2).

| Comparisons of all indices between the bypass and contralateral sides
The significance of all indices between the bypass and contralateral sides is shown in Table 2. Furthermore, line charts over time are shown, including the STA-PB and STA-FB, in Figure 5. The contralateral side could be considered an alternative control reference for bypass results. These results confirm this hypothesis. All ultrasonography indices in STA-PB significantly differed between the bypass and contralateral sides (all p < 0.05). Particularly after surgery, the pattern was similar to the comparison between the STA-PB and STA-FB at the bypass side. Significant differences were observed in the STA-FB between the bypass and contralateral sides; however, no specific pattern is shown in Figure 5.

| Associated factors of postoperative flow on days 1 and 7
In the correlation coefficient analysis, no significance was found be-  Table 3 and Table S4).

| Postoperative complications
Among the 81 patients, the overall incidence of postoperative complications was approximately 11.1% (nine patients), including seizure, subcutaneous hematoma, transient aphasia, and pulmonary infection in three, two, two, and two patients, respectively.

| Clinical outcome
In our study, all patients were followed up via telephone interviews or clinic visits. In total, 78 (96.3%) patients had mRS scores ranging from 0 to 2, and three patients had mRS scores >3( Table 4). One patient had mRS scores of 4 at discharge and 5 at 2 years after surgery.

| DISCUSS ION
In our study, we performed quantitative ultrasonography in pa- need to be used, which increases the risk of occlusion. Therefore, the STA can be used as a donor artery for EC-IC bypass surgery and can provide adequate blood supply to the brain. According  (Table 3 and Table S4). However, the diameter of the anastomosis could not be measured.  embolization can also undergo STA-MCA bypass surgery in combination with endovascular exclusion. The use of this method, called hybrid surgery, to treat complex or giant intracranial aneurysms has also been accepted by neurosurgeons increasingly. [32][33][34] Our previous study revealed that STA grafts showed good patency after STA-MCA bypass surgery in patients with intracranial aneurysms and that the mean flow could be increased above 100 mL/min with these grafts. 35 We >15%, the patency of the anastomosis on DSA was good. 36 Hirai et al.
demonstrated that duplex ultrasonography was available for evaluating the postsurgical patency of bypass flow and regional cerebral blood flow (rCBF) in the ipsilateral MCA territory. 37 In this study, we Our study has some limitations. First, the number of patients enrolled in our study was small, particularly those with aneurysm.
Increasing the proportion of patients in this study would be beneficial for our study. Second, to reduce human measurement and machine errors, patients could only return to our center for quantitative ultrasonography testing, resulting in a lack of long-term data for most patients. Finally, we did not monitor the flow during surgery.
If the flow can be detected intraoperatively, we can adjust the size of the anastomosis according to the intraoperative flow and analyze the effect of the intraoperative flow size on the short-and long-term postoperative periods.

| CON CLUS ION
The STA can be used as a donor artery for EC-IC bypass surgery and can provide a robust blood supply to the brain. The mean STA flow rate can reach 116.74 mL/min and 118.44 mL/min 1 day and 1 week postoperatively, respectively, and can also be maintained at 56.2 mL/min for >6 months after surgery.

CO N FLI C T O F I NTER E S T S TATEM ENT
The authors declare that this study was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

DATA AVA I L A B I L I T Y S TAT E M E N T
Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

E TH I C S A PPROVA L A N D CO N S E NT TO PA RTI CI PATE
All procedures involving human participants were performed in ac-