Quantitative Assessment of Regional Cerebral Blood Flow Changes Following Extracranial-Intracranial Bypass Using SPECT: A Single-Center Retrospective Study

1. Introduction

Extracranial-intracranial (EC-IC) arterial bypass has been utilized to treat various intracranial pathologies, including moyamoya disease, arterial stenosis or occlusion, complex aneurysms not amenable to endovascular treatment, and secondary cerebral ischemia [1,2]. In patients with carotid stenosis or occlusion, bypass improves cerebral blood flow (CBF) at rest and augments cerebrovascular reserve during periods of increased metabolic demand [2,3,4]. Consequently, it can reduce further ischemic events, reverse the vascular steal phenomenon, and potentially enhance long-term neurocognitive function in appropriately selected patients [5].

Because EC-IC bypass may reduce stroke risk, restore cortical thickness, and improve cognitive outcomes, objective pre- and postoperative hemodynamic monitoring is essential to confirm revascularization success [6,7]. The objective of this study was to investigate the impact of STA-MCA bypass on regional cerebral blood flow (rCBF) using single-photon emission computed tomography (SPECT) as a semi-quantitative surrogate marker, with particular focus on the basal ganglia and temporal regions—areas critical for motor, cognitive, and executive functions [8]. We further examined whether surgical laterality influenced the pattern of perfusion improvement (ipsilateral vs. contralateral regions).

2. Materials and Methods

2.1. Patients and Surgical Procedure

Patients who underwent pre- and postoperative brain computed tomography angiography (CTA) and rCBF-SPECT studies at our institution between June 2018 and June 2022 were retrospectively selected. This study was approved by the institutional research ethics board, and all patients provided informed consent.

Inclusion criteria were: (1) patients with intracranial steno-occlusive disease or moyamoya disease who received either unilateral or bilateral superficial temporal artery to middle cerebral artery (STA-MCA) EC-IC bypass; (2) availability of preoperative CTA and at least one postoperative CTA; and (3) availability of preoperative rCBF-SPECT and at least one postoperative rCBF-SPECT study. Patients with missing imaging studies or loss to follow-up were excluded.

2.2. Image Processing and rCBF Measurement

We focused on the basal ganglia and temporal regions for rCBF assessment, as these areas are crucial for motor control, cognition, and executive function [6].

The detailed image processing pipeline is illustrated in Figure 1 and consists of the following steps:

A. Slice Selection: Preoperative and postoperative SPECT images were co-registered with corresponding CTA when available. Two independent observers (one neurosurgeon and one neuroradiologist) selected the most representative axial slice at the level of the basal ganglia (approximately at the anterior commissure–posterior commissure line) and the temporal lobes, ensuring clear visualization of the lenticulostriate territories and Sylvian fissure.

B. Region of Interest (ROI) Annotation using Labelme: Selected DICOM images were converted to 8-bit grayscale PNG format and imported into Labelme (version 5.0.1, an open-source image annotation tool developed by wkentaro). Polygonal annotations were manually drawn to delineate areas of detectable tracer uptake.

C. Labelme Annotation Protocol:

A. Use the “Create Polygons” tool (shortcut: Ctrl + N) to trace the boundaries of the bilateral basal ganglia (caudate nucleus, putamen, and globus pallidus) and temporal lobes (superior, middle, and inferior temporal gyri).

B. Annotations were performed in a blinded manner with respect to pre- or postoperative status to minimize bias.

C. For each region, label names were assigned as BG_Left, BG_Right, Temp_Left, and Temp_Right.

D. Practical techniques included: using mouse wheel for precise zooming, holding the space bar to pan the image, Ctrl + Z for undo, and right-click to close the polygon. For regions with fuzzy boundaries (common in SPECT), a conservative 1–2 pixel outward adjustment was applied, followed by manual vertex editing. Newer versions of Labelme with Segment Anything Model 2 (SAM2) integration were optionally used for initial automatic segmentation, followed by manual refinement to ensure anatomical accuracy.

D. Binary Mask Generation and Edge Detection: Exported JSON files containing polygon coordinates were parsed using custom Python scripts (Python 3.9 with OpenCV 4.5). Polygon coordinates were converted into binary mask images (white ROI on black background). Contours were extracted using the Canny edge detection algorithm (low threshold = 50, high threshold = 150, aperture size = 3), with parameters optimized through pilot testing to balance sensitivity and noise reduction.

E. Area Calculation: The area enclosed by each closed contour was computed using Green’s theorem (shoelace formula):

$$A={\displaystyle \frac{1}{2}}\left|{\displaystyle \sum _{i=1}^{n-1}}\left(x_i{y}_{i+1}-x_{i+1}{y}_i\right)+\left(x_n{y}_1-x_1{y}_n\right)\right|$$

This mathematical approach provides sub-pixel accuracy for irregular anatomical regions.

F. Normalization: To compensate for variations in head positioning, slice angulation, and global tracer uptake, the ROI area was normalized by dividing it by the total brain area (excluding ventricles and extracerebral spaces) on the same axial slice, yielding a proportional perfusion area metric (unitless ratio).

G. Reliability Assessment: Intra-rater and inter-rater reliability were evaluated on 20 randomly selected images (10 pre-operative and 10 post-operative). The intraclass correlation coefficient (ICC) exceeded 0.88 for both basal ganglia and temporal regions, indicating excellent reproducibility.

This pragmatic semi-quantitative method using open-source tools offers a practical, anatomically specific, and visually intuitive approach for clinical hemodynamic assessment without requiring absolute quantification or complex arterial input functions. Custom Python scripts used for data processing are available from the corresponding author upon reasonable request.

We focused on the basal ganglia and temporal regions for rCBF assessment, as these areas are crucial for motor control, cognition, and executive function and are commonly affected in steno-occlusive cerebrovascular disease [6,8]. Semi-quantitative analysis was performed on representative axial slices of rCBF-SPECT images.

2.3. Surgical Intervention and Follow-Up

All patients underwent direct STA-MCA bypass via end-to-side anastomosis of the parietal branch of the superficial temporal artery to a cortical M4 branch of the middle cerebral artery. Our standard postoperative follow-up included clinical evaluation, CTA assessment of anastomosis patency (graded as patent or occluded using axial thin-slice maximum intensity projection reconstructions), and rCBF-SPECT for hemodynamic assessment. All imaging was independently evaluated by two experienced neuroradiologists or neurosurgeons.

2.4. Statistical Analysis

Categorical variables are presented as counts and percentages. Continuous variables with normal distribution are expressed as mean ± standard deviation (SD). Paired pre- and postoperative comparisons were performed using the paired t-test, with mean differences (MD) and 95% confidence intervals (CI) reported. Subgroup analyses were conducted according to surgical laterality (left-sided vs right-sided surgery) and, for unilateral cases, according to ipsilateral versus contralateral regions. A p-value < 0.05 was considered statistically significant. Analyses were performed using MedCalc for Windows (version 22.032, MedCalc Software, Ostend, Belgium).

3. Results

Fifteen patients were included. The mean age was 56 ± 15.7 years, and 40% (n = 6) were female. Surgical indications were moyamoya disease (n = 3, 20%) and arterial stenosis or occlusion (n = 12, 80%). Fourteen patients underwent unilateral STA-MCA bypass, and one patient received bilateral bypasses, resulting in a total of 16 anastomoses. All anastomoses were patent intraoperatively and remained patent on postoperative CTA. One patient experienced a recurrent ischemic stroke in the left temporal cortex nine months after left-sided bypass surgery; no other major perioperative complications were observed.

Table 1. Patient demographics, comorbidities, and surgical characteristics (n = 15).

Variable	Value
Age, years (mean ± SD)	56 ± 15.7
Sex, n (%)
Male	9 (60)
Female	6 (40)
Comorbidities, n (%)
Hypertension	6 (40)
Diabetes mellitus	9 (60)
Hyperlipidemia	6 (40)
Atrial fibrillation	0 (0)
Coronary artery disease	2 (13.3)
Prior ischemic stroke	13 (86.7)
Prior hemorrhagic stroke	1 (6.7)
Chronic renal failure (eGFR <60)	0 (0)
Antiplatelet therapy	10 (66.7)
Diagnosis, n (%)
Moyamoya disease	3 (20)
Arterial stenosis/occlusion	12 (80)
Surgical laterality, n
Unilateral	14
Bilateral	1
Total anastomoses	16 (all patent)

Table 1. Patient demographics, comorbidities, and surgical characteristics (n = 15).

Variable	Value
Age, years (mean ± SD)	56 ± 15.7
Sex, n (%)
Male	9 (60)
Female	6 (40)
Comorbidities, n (%)
Hypertension	6 (40)
Diabetes mellitus	9 (60)
Hyperlipidemia	6 (40)
Atrial fibrillation	0 (0)
Coronary artery disease	2 (13.3)
Prior ischemic stroke	13 (86.7)
Prior hemorrhagic stroke	1 (6.7)
Chronic renal failure (eGFR <60)	0 (0)
Antiplatelet therapy	10 (66.7)
Diagnosis, n (%)
Moyamoya disease	3 (20)
Arterial stenosis/occlusion	12 (80)
Surgical laterality, n
Unilateral	14
Bilateral	1
Total anastomoses	16 (all patent)

Quantitative analysis of proportional perfusion area on rCBF-SPECT demonstrated statistically significant postoperative improvement in both regions of interest. For the basal ganglia, the mean difference (MD) was +0.24 (95% CI 0.13–0.35, p = 0.0003). For the temporal regions, the MD was +0.34 (95% CI 0.08–0.60, p = 0.0131). (Figure 2.)

In unilateral cases (n = 14), there was no statistically significant difference in basal ganglia perfusion improvement between ipsilateral and contralateral sides (overall ipsilateral Δ +0.128 vs contralateral Δ +0.130, p = 0.839) (Table 2.) Similar patterns were observed for the temporal regions. These findings suggest that the hemodynamic benefit of STA-MCA bypass extends beyond the immediate surgical territory.

4. Discussion

Low-flow extracranial-intracranial (EC-IC) arterial bypass, particularly superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis, remains an important revascularization strategy for carefully selected patients with moyamoya disease or atherosclerotic steno-occlusive disease who exhibit impaired cerebrovascular reserve [1,2,10,11]. In the present study, we achieved a 100% postoperative patency rate across 16 anastomoses, which is comparable to or exceeds the 95–99% patency rates reported in contemporary high-volume cerebrovascular centers [12,13].

The core hemodynamic finding of this study—statistically significant postoperative expansion of the proportional perfusion area on semi-quantitative SPECT, with particularly robust and consistent gains in the basal ganglia—aligns well with multiple prior investigations employing various perfusion imaging modalities, including SPECT, CT perfusion, and arterial spin labeling MRI [14,15,16]. Anatomically, direct anastomosis to a cortical M4 branch primarily augments the distal MCA territory. However, the pronounced improvement observed in the basal ganglia, which are predominantly supplied by the lenticulostriate perforators arising from the M1 segment, is noteworthy. This phenomenon likely results from a combination of mechanisms: (1) overall increase in hemispheric inflow leading to enhanced pressure gradients across perforators, (2) reversal of the vascular steal phenomenon, (3) recruitment of leptomeningeal and pial collaterals, and (4) restoration of cerebral autoregulation capacity [17,18].

Consistent with Mesiwala et al. [2], who reported postoperative cerebral blood flow improvement in approximately 80% of patients after STA-MCA bypass, and Li et al. [4], who demonstrated significant increases in regional cerebral blood flow using perfusion-weighted imaging, our semi-quantitative SPECT analysis revealed directional improvement in 13 of 15 patients in the basal ganglia region. Furthermore, Ha et al. [19] reported that increases in normalized cerebral blood flow on arterial spin labeling MRI correlated with the degree of postoperative neovascularization in pediatric moyamoya disease, supporting the notion that perfusion imaging can serve as a reliable surrogate marker of revascularization success.

In our subgroup analysis (Table 2), improvement in basal ganglia perfusion was similar between patients undergoing left-sided (mean Δ +0.23) and right-sided (mean Δ +0.28) surgery. More importantly, in unilateral cases, there was no statistically significant difference between ipsilateral and contralateral basal ganglia improvement (overall ipsilateral Δ +0.128 vs contralateral Δ +0.130, p = 0.839). This finding supports the concept that the hemodynamic benefit of STA-MCA bypass is not limited to the surgical side but reflects a more global hemispheric perfusion augmentation [19,20], likely mediated by increased overall inflow and collateral recruitment, rather than being limited to the ipsilateral surgical territory. This may reflect the indirect effects of overall hemispheric blood flow increase and collateral compensation.

The basal ganglia play a pivotal role in cognitive gating, executive function, motor control, and emotional regulation through their complex cortico-striato-thalamo-cortical loops [6,21]. Therefore, the reliable perfusion augmentation observed in this deep gray matter structure carries important potential clinical implications. These findings are consistent with Sasoh et al. [6], who observed partial alleviation of cognitive impairment following EC-IC bypass in patients with hemodynamic cerebral ischemia, particularly among those with shorter symptom duration. Several recent cohort studies have also documented postoperative improvements in Montreal Cognitive Assessment (MoCA) scores and other neuropsychological domains following EC-IC bypass surgery, especially in patients with shorter symptom duration and preoperative reversible perfusion deficits [11,22,23,24].

Although the landmark Carotid Occlusion Surgery Study (COSS) demonstrated no overall benefit of EC-IC bypass over best medical management in patients with symptomatic unilateral internal carotid artery occlusion and misery perfusion [3], subsequent subgroup analyses and selective case series suggest that highly selected patients with recurrent ischemic events despite optimal medical therapy and objective evidence of severe hemodynamic impairment may still derive substantial benefit [26,27,28]. Our real-world Asian cohort, which included both moyamoya disease and atherosclerotic pathology, adds valuable data supporting the individualized application of bypass surgery in appropriately selected patients.

Methodologically, the custom semi-quantitative area-proportion method using Labelme, Canny edge detection, and Green’s theorem offers practical advantages in daily clinical settings. It is relatively simple, cost-effective, and provides anatomically specific metrics without requiring absolute quantification. However, it remains two-dimensional and operator-dependent. Future studies should validate this approach against fully quantitative techniques such as PET or ASL-MRI [29].

Limitations of this study include the small sample size, retrospective single-center design, clinical heterogeneity (mixed moyamoya and atherosclerotic cases), absence of a control group, lack of standardized long-term neuropsychological outcomes, and the semi-quantitative nature of the SPECT analysis. Strengths include complete paired imaging follow-up, 100% bypass patency, blinded annotation, rigorous reliability testing (ICC > 0.88), and detailed subgroup analysis including ipsilateral versus contralateral comparisons.

Future directions include larger prospective multicenter studies integrating quantitative perfusion imaging, comprehensive neuropsychological assessment, long-term stroke-free survival data, and comparative effectiveness research between direct, indirect, and combined bypass techniques. Identification of reliable hemodynamic and clinical responders will further refine patient selection criteria in contemporary revascularization practice [30].

5. Conclusions

STA-MCA bypass was associated with objective improvement in regional cerebral blood flow on semi-quantitative SPECT, with consistent benefits observed in the basal ganglia. Improvement was similar regardless of surgical laterality, and in unilateral cases there was no significant difference between ipsilateral and contralateral basal ganglia perfusion gains. These findings support the concept of a global hemispheric perfusion augmentation mechanism, likely mediated by increased overall inflow, reversal of steal phenomenon, and enhanced collateral circulation, rather than purely localized effects. SPECT, even with pragmatic semi-quantitative methods, remains useful for perioperative monitoring. Future prospective multicenter studies incorporating quantitative perfusion imaging, standardized neuropsychological assessments, and long-term clinical outcomes are warranted to further validate these observations, refine patient selection criteria, and optimize revascularization strategies in cerebrovascular revascularization practice.