Arterial spin labeling for moyamoya angiopathy: A preoperative and postoperative evaluation method

2.1 Patient selection

A retrospective cohort study was conducted to select patients with MMA from the Neurosurgery Moyamoya Disease Diagnosis and Treatment Center from September 2019 to August 2021. The random number method was used for selection. All the patients were diagnosed using digital subtraction angiography (DSA). The diagnostic criteria were as follows: (1) bilateral ICA end and/or ACA and/or MCA initial segment stenosis or occlusion and (2) an abnormal vascular network at the skull base appearing in the arterial phase [17]. Angiography results were evaluated by two neurointerventional physicians.

The inclusion criteria were as follows: (1) patient with stable condition before the operation and no new cerebral hemorrhage, cerebral infarction, frequent transient ischemic attacks (>2 times per week), and other related neurological symptoms; (2) patient underwent the first CBF reconstruction surgery (“superficial temporal artery (STA)–middle cerebral artery (MCA) bypass and encephalo–duro–myo–synangiosis”) in our hospital, performed by the same surgeon; (3) patient was treated before surgery, and at 1 week and 6 months after surgery; (4) the MRI machine in our hospital performed ASL perfusion imaging monitoring; and (5) patient agreed to perform ASL assessment and signed an informed consent form.

The exclusion criteria were as follows: (1) patients with Graves’ disease, antiphospholipid antibody syndrome, systemic vasculitis, Sjogren’s syndrome, systemic atherosclerosis, and other clear comorbidities; (2) DSA examination of patients with MMA accompanied by other brain vascular diseases, such as aneurysms and cerebrovascular malformations; (3) inability to perform ASL imaging due to personal constitutions, such as mental abnormalities, claustrophobia, cognitive impairment; (4) the quality of ASL imaging of the patient was poor or does not perform standard imaging; (5) the patient’s clinical data were missing or incomplete; and (6) The patient did not develop serious postoperative complications, such as massive cerebral infarction, cerebral hemorrhage, or grand mal seizure (Figure 1).

Figure 1

Patient inclusion flowchart.

2.2 Surgical procedure

After general anesthesia, according to the individual conditions of the patient, blood pressure and partial pressure of carbon dioxide were controlled [18,19,20]. The extended pterional approach was used; the temporal muscle and STA were carefully separated, the bone flap was removed, and the dura mater was carefully cut to expose the brain surface. A microscope (ZEISS) was used to perform a fluorescence contrast test to understand the blood flow of the distal middle cerebral artery on the brain surface and select the appropriate blood vessels. The recipient blood vessel and STA branch were wrapped and soaked with papaverine solution to prevent vasospasm. Subsequently, a temporary aneurysm clip was used to clamp the blood supply on both sides of the recipient blood vessel and proximal end of the STA branch. The frontal parietal surface was examined at the distal end of the body vessel and the STA branch. After bypass was completed, intraoperative angiography was performed to check the patency and flow of the reconstructed vessel. Finally, the separated and intact temporal muscles were directly applied to the parietal and frontal brain surfaces, and the dura mater was turned over and applied to the brain surface to complete the combined cerebral revascularization operation [21,22].

2.3 ASL image acquisition

The ASL technology used a Philips Ingenia 3.0T magnetic resonance scanner (Philips, the Netherlands). The patient was placed in the supine position, while the head was properly fixed, and a 32-channel head special coil was used. The scanning baseline was the front and back joint connection, and the scanning sequence was axis T1WI, axis T2WI, axis T2 FLAIR, and pseudo-continuous arterial spin labeling (pCASL). The scanning parameters of the pCASL sequence were as follows: repetition time = 4,364 ms; echo time = 12 ms; layer thickness, 6 mm; field of view, 240 mm × 240 mm; matrix, 64 × 60; delay time after marking, 2,000 ms; number of excitations, 1; and scanning time, 306 s. The CereFlow ASL image software (Animage Technology, China) was used for post-image processing. The processing flow was as follows: (1) the ASL original map calculated CBF through a single-chamber model; (2) the cerebral perfusion parameter map was standardized to the MNI brain template space [23]; (3) the brain atlas of the standard grading system was covered based on the Alberta Stroke Program Early CT Score (ASPECT) of Alberta stroke procedures, covering ten regional divisions of the MCA blood supply area at two levels: the nucleus level (thalamus and striatum plane) divided into seven areas: medial prearterial cortex (M1), middle cerebral artery extrainsular cortical area (M2), posterior middle cerebral cortex (M3), insula, lentiform nucleus, caudate nucleus, capsula interna, and the level above the nucleus (add cmMo at the nucleus level). There were three areas of the middle cerebral artery cortex above M1 (M4), the middle cerebral artery cortex above M2 (M5), and the middle cerebral artery cortex above M3 (M6) [24]. (4) After covering the brain atlas, the mean value of each area in each brain perfusion parameter map was analyzed. The absolute quantitative CBF value of the aspect area on the operation side was automatically obtained.

2.4 Revascularization classification

To assess the revascularization effect, Matsushima grading [25] was used to classify and compare the patients into two groups. First, the hypovascular group had the following characteristics: (1) no obvious change in the diameter of the bypass vessel or obvious intracranial compensation; (2) the bypass vessel was thickened or a small amount of compensation was performed on the brain, and (3) the compensation of the MCA area on the operation side was less than 1/3. Second, the hypervascular group included the following: (1) the bypass vessel compensated for the cranium, and for the MCA area between 1/3 and 2/3 on the operation side; and (2) the bypass vessel compensated for more than 2/3 of the MCA area on the operation side. According to the Alberta stroke grade and CBF value, the stroke score was given (Table 1).

Albert stroke score was 10 points, each area lower than normal blood flow (CBF <30 mL/100 g/min) [26] was defined as the perfusion defect area, and the corresponding brain area score was reduced by 1 point, and the final score was calculated.

2.5 Statistical analysis

All data were entered and analyzed using SPSS (version 26.0, IBM, USA). Corresponding statistical analysis of the general clinical data and CBF data was performed. Measurement data (such as ASL monitoring time and age) and data conforming to the normal distribution are expressed as mean value ± standard deviation ( x ̅ ± s ), and paired t-tests were used to analyze the data. The measurement data that did not conform to the normal distribution adopted the median/quartile (M/P25, P75) and were analyzed using the Wilcoxon non-parametric test. The enumeration data (sex, clinical manifestations, etc.) were analyzed using the chi-square test and Fisher’s exact test. Grade data (such as Suzuki staging) were tested using a rank-sum test. Statistical significance was set at P ≤ 0.05.

1. Ethical approval: The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ institutional review board or equivalent committee. This study was reviewed and approved by the Ethics Committee of Henan Provincial People's Hosptial (2020183).

2. Informed consent: Informed consent has been obtained from all individuals included in this study and the clinical data were kept strictly confidential.

3.1 Demographics

Based on the inclusion and exclusion criteria, 51 patients with 90 hemispheres were included in this study. Table 1 summarizes the baseline participants and clinical characteristics of MMA. The mean age on admission was 41.68 ± 11.38 years and men (60.78%) constituted the majority of the cohort. The clinical presentation showed onset symptoms of ischemia in 37 (72.54%) patients and intracranial hemorrhage in 14 (27.46%) patients. The ASL monitoring time was recorded on three postoperative periods: first, 4.39 ± 1.49 days; second, 6.26 ± 0.67 days; and third, 181.65 ± 10.93 days (Table 2).

3.2 ASL perfusion data

The CBF values of each region of the cerebral hemisphere before the operation were: insula, 29.06 ± 9.85; M1, 26.06 ± 11.67; M2, 27.74 ± 10.24; M3, 27.29 ± 9.70; M4, 24.98 ± 12.18; M5, 25.71 ± 9.97; M6, 27.25 ± 11.35; caudate nucleus, 21.67 ± 9.34; inner capsule, 20.85 ± 6.81; and lenticular nucleus, 29.22 ± 12.09.

The CBF values of each region of the cerebral hemisphere after 1 week of operation on the surgical side were as follows: insula, 47.74 ± 22.50; M1, 32.78 ± 14.02; M2, 36.14 ± 12.81; M3, 34.35 ± 14.53; M4, 33.72 ± 15.34; M5, 33.50 ± 14.62; M6, 35.32 ± 16.28; caudate nucleus, 21.85 ± 6.76; inner capsule, 24.63 ± 7.39; and lenticular nucleus, 33.14 ± 11.29.

The CBF values of each region of the cerebral hemisphere on the surgical side at 6 months after the operation were: insula, 34.52 ± 12.19; M1, 29.51 ± 13.47; M2, 33.78 ± 15.31; M3, 33.15 ± 11.09; M4, 29.14 ± 13.70; M5, 29.07 ± 12.71; M6, 31.38 ± 11.24; caudate nucleus, 20.78 ± 7.90; inner capsule, 19.10 ± 5.39; and lenticular nucleus, 24.84 ± 5.74.

After applying the paired t-test to the three sets of data, the preoperative and 1week postoperative CBF value comparison showed that there were statistical differences in eight regions: the insula, M1, M2, M3, M4, M5, M6, and inner capsule. There was no statistical difference between the caudate nucleus and lenticular nucleus. Comparison of the preoperative and 6 months postoperative CBF values showed statistical differences in seven regions: the insula, M1, M2, M3, M4, M5, and M6. There was no statistical difference in the caudate nucleus, inner capsule, and lenticular nucleus (Figure 2).

Figure 2

Quantitative CBF values in each area of enrolled patients were evaluated under ASPECT partitioning criteria. (a and b) The CBF values of each cerebral cortex region were statistically different (preoperation vs 1 week after surgery, preoperation vs 6 months after surgery). (c and d) The CBF values of each subcortical region were statistically different (preoperation vs 1 week after surgery, preoperation vs 6 months after surgery). Paired t test was used for comparison between the two groups, and P ≤ 0.05 was considered to be statistically significant. ns: P > 0.05, *: P ≤ 0.05, **: P < 0.01, ***: P < 0.001.

3.3 Relationship between ASPECT score and the effect of postoperative cerebrovascular reconstruction

According to the Matsushima classification, the 90 hemispheres were divided into 2 groups: 69 in the hypovascular group and 21 in the hypervascular group. Statistical differences in variables between the groups were compared. There was no statistically significant difference in the general clinical symptoms between the two groups (P > 0.05). Among the three Alberta scores, the preoperative Alberta score differed between the two groups (P < 0.05). At the same time, we compared the changes in the mRS scores between the two groups before and after surgery. There was a significant difference between the two groups before surgery (P ≤ 0.05) (Table 3, Figure 3).

Figure 3

The postoperative CBF of the patients reach the normal level under different vascular conditions. (a–c) Relationship between ASL images and postoperative neovascularization network density in three typical patients. The Alberta score of the three patients decreased gradually before surgery, and the neovascularization network density increased gradually after surgery.

4.1 Limitations

The aim of this study was to provide data that ASL technology can contribute as a practical and significant method for patients with MMA and can play an auxiliary role in monitoring postoperative complications. However, owing to the small sample size and short follow-up time, the results may be biased. It is still necessary to expand the sample size and conduct more long-term follow-up monitoring of patients to continue to explore the application value of ASL technology in MMA.