INTRODUCTION
The cerebral arterial circle (CAC) represents a complex arterial anastomotic chain between the carotid and vertebrobasilar system and consists of nine vascular components: paired precommunicating segment of the posterior cerebral artery (PCA–P1), paired posterior communicating artery (PCoA), paired cerebral segment of the internal carotid artery (ICA), paired precommunicating segment of the anterior cerebral artery (ACA–A1) and unpaired anterior communicating artery (ACoA) [40].
All arterial components of CAC and their (eventual) variations are developed during the prenatal life, at the stage of the embryonic length of 40 mm, that is ovulation age of 52 days, as cited by Burbank and Morris [5]. After that, the arteries change in terms of their diameter, which is conditioned by numerous factors, primarily hemodynamic [11].
It is common for communicating arteries to have the smallest diameter and to play a role in the redistribution of blood between neighbouring arteries of larger calibre [14]. Based on the ratio of the diameters of the arteries, the types of the posterior segment of CAC are described. A less complex typification refers to the adult, transitory and fetal type [34], while a more complex typification was given by Vasović et al. [38] and 59 types of the posterior segment of the CAC were described.
The morphological types of CAC are very important, but the functionally critical feature of the CAC artery is its hypoplasia. There is no exact definition of CAC arterial hypoplasia in the available literature. Functional testing of arterial diameters emphasizes a diameter of 1 mm as a critical value below which the blood vessel is not competent to provide adequate collateral circulation if there is an interruption of blood flow in one of the main neighbouring arteries [6, 26]. Papantchev et al. [27, 28] defined ischaemic zones of the central nervous system in 6, that is 7 (sub)types of CAC that are not able to provide adequate blood flow during unilateral selective perfusion (cannulation of the brachiocephalic trunk) in surgical procedures on the aortic arch.
Cadaveric studies show morphologically small variations, but clinical practice always relies on radiological examination methods. Two large cadaveric studies showed the frequency of incomplete CAC 6.32% [39] and 10.66% [13], while in computed tomography angiography (CTA) studies these percentages were 29% [19], 62.8% [23], 69.2% [20], 77.5% [7], 89% [37]. These data indicate that a certain percentage of hypoplastic arteries in CTA studies are shown as aplastic. It is obvious that the technical capabilities of CTA are still not at the level to be able to visualize structures of sufficiently small dimensions.
The mentioned research on the morphology of CAC and the status of the arteries that make it up represent only a part of the published studies on this topic, but they indicate their great clinical importance. Although arterial hypoplasia as a term has been known for a long time, no consensus has been reached regarding its definition, which contributes to additional differences in the incidence of its occurrence in the available literature.
Due to the differences in the definition of the term hypoplasia and the large differences in the literature data on the frequency of hypoplastic (and aplastic) CAC arteries, this paper aims to suggest criterion for hypoplasia based on the physiological contribution and anatomical presentation, determine the frequency of hypoplastic blood vessels in a cadaveric study and critically examine the possibility of their visualization by CTA.
MATERIALS AND METHODS
The research was performed on 400 human cadavers of both genders and different ages (from neonates to 95). Cadavers were routinely autopsied due to different causes of death at the Department of Forensic Medicine.
Each single brain base with blood vessels of all cadaveric cases was recorded on the photo film and schematically presented in the workbook. The angioarchitecture of the CAC was inspected macroscopically and under the magnifying glass, and after that, the outer diameters of the cerebral arteries were calculated by the digital images processing in the ImageJ program (http://rsb.info.nih.gov/ij/index.html). The determination of the arteries and their variation was performed according to the recommendations of Yasargil [40].
The comparison of the obtained values was interpreted regarding the literature data on the criteria for hypoplasia, which were presented previously. After that, consideration was given to the visibility of hypoplastic arteries regarding the limit value of CTA sensitivity, for which a cut-off value of 0.6 mm was taken as an approximate value of the slice thickness (0.625 mm) in CTA [7, 37].
Statistical analysis
Statistical analysis was performed in SPSS ver. 23.0 (IBM Corp. Released 2015. IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp.). Comparison between groups tested by using Student’s t-test or Mann-Whitney U test (depends on the normality of values in groups) with the level of significance at p < 0.05. The Shapiro–Wilk test was a test of normality.
RESULTS
Four neonates and a 5-year-old child were excluded from the study because their cerebral arteries were small in diameter, so they were considered an exception compared to the statistical average. The youngest of the remaining cases was a 16-year-old girl. Further analysis included 395 cases (171 female and 224 male) with an average age of 65.7 ± 17.5 years.
The average values and standard deviations of the measured diameters of the arteries of CAC, as well as their maximum and minimum values, are shown in Table 1. No statistically significant difference was found between the diameter values of the arteries on opposite sides. The criterion for hypoplasia chosen for this study is a diameter value of less than 1 mm. Among the hypoplastic arteries, those that had a diameter of less than 0.6 mm were noted, assuming that such arteries would not be visible using the CTA examination method. The percentage of hypoplastic CAC arteries and arteries with a diameter of less than 0.6 mm is given in Table 1.
|
CAC components |
PCA–P1 dex. |
PCA–P1 sin. |
PCoA dex. |
PCoA sin. |
ICA dex. |
ICA sin. |
ACA–A1 dex. |
ACA–A1 sin. |
ACoA |
|
Mean |
2.066 |
2.066 |
1.255 |
1.314 |
3.715 |
3.75 |
2.087 |
2.136 |
1.657 |
|
SD |
0.617 |
0.604 |
0.701 |
0.71 |
0.863 |
0.802 |
0.476 |
0.477 |
0.66 |
|
p |
n.s. |
n.s |
n.s. |
n.s. |
|||||
|
Max. |
4.048 |
3.459 |
4.196 |
3.527 |
7.128 |
6.625 |
3.31 |
3.408 |
3.985 |
|
Min. |
0.47 |
0.335 |
0.316 |
0.361 |
1.264 |
1.527 |
0.525 |
1.114 |
0.452 |
|
< 1 mm (%) |
4.2 |
3.0 |
44.3 |
44.9 |
0.0 |
0.0 |
2.4 |
0.0 |
14.4 |
|
< 0.6 mm (%) |
0.6 |
0.6 |
6.6 |
11.4 |
0.0 |
0.0 |
0.6 |
0.0 |
1.2 |
The highest percentage of hypoplastic diameters was recorded on the PCoA — 44.3% on the right and 44.9% on the left side. In 28.14% of cases, both PCoAs had a hypoplastic diameter (Fig. 1).
The hypoplastic diameter was also recorded in 14.4% of ACoA, but it should be emphasized that only cases with unique ACoA trunks were analysed. This artery is extremely variable and in a third of the cases on the examined material, it is shown in the form of partial or total duplication, triplication, quadruplication, fenestration, and rete form. In variable forms, almost always one of the segments of the variation is hypoplastic. Communicating arteries also had the highest frequency of diameters less than 0.6 mm. Internal carotid arteries were not hypoplastic in any case, but in 1.8% of cases on the right side and 1.2% of cases on the left side, they had a diameter of less than 2 mm.
The absence of one or two CAC components was noted in 5.1% of cases. In 12.4% of cases, there was an excess artery of the posterior segment of the CAC, while only in 3 cases (0.75%) there was simultaneously the absence of PCoA on the right side and the presence of an excess artery of the posterior segment on the left side (Fig. 2). This excess artery had a diameter of less than 1 mm in 89.8% of cases, and a diameter of less than 0.6% in 44.9% of cases.
In the examined series, CAC with all arteries larger than 1 mm in diameter was noted in only 15.2% of cases and these CACs will be visible as complete CAC at CTA scans, while cases with an arterial diameter of less than 0.6 mm and cases with truly aplastic CAC segments were 30.6% of all cases.
The various criteria for arterial hypoplasia in CAC from the available literature, as well as the major results presented in that studies, are shown in Table 2. After summing up cases with aplasia and hypoplasia of arteries and calculating the frequency of cases with hypoplasia and aplasia in CAC in the available literature, it was determined that studies on cadaveric material recorded the occurrence of hypoplasia statistically significantly more often (p < 0.05), while studies in which CTA was used statistically significantly more often noted the appearance of aplasia (p < 0.001).
|
The criteria for hypoplasia |
Number of subjects/methodology of the study |
Incidence of hypoplastic arteries and/or aplastic arteries (incomplete CAC) |
Year of the study |
|
< 1.5 mm ACA–A1 and ACoA |
50/cadavers |
10% hypoplastic ACA–A1; 44% hypoplastic ACoA; 0.5% ACA–A1 < 1 mm; 16% ACoA < 1 mm |
1976 [30] |
|
< 1 mm PCoA and ACoA |
137/cadavers |
46% hypoplastic PCoA; 3.6% hypoplastic ACoA |
1967 [3] |
|
≤ 1 mm |
143/cadavers |
22.37% complete CACs without hypoplastic arteries; 25.17% bilateral hypoplastic PCoA; 32.16% unilateral hypoplastic PCoA; 1.39% hypoplastic ACoA; 6.29% unilateral hypoplastic PCA–P1; 4.19% bilateral hypoplastic PCoA and hypoplastic ACoA |
2013 [39] |
|
< 1 mm |
102/cadavers |
7% unilateral aplastic PCoA; bilateral aplastic PCoA 3%; 27% unilateral hypoplastic PCoA; 33% bilateral hypoplastic PCoA; 7% hypoplastic PCA–P1 |
2006 [10] |
|
112/cadavers |
Defined 6 types of CAC with specific hypoplastic arteries in 42.4% of cases |
2007 [27] |
|
|
1000/cadavers |
1.8% aplastic ACoA; 2.1% hypoplastic ACoA; 1% aplastic PCoA; 16.7% hypoplastic PCoA; 0.4% aplastic ACA–A1; 1.7% hypoplastic ACA–A1 |
2008 [18] |
|
|
102/cadavers |
10.8% incomplete CAC; 10.8% hypoplastic ACoA; 1% hypoplastic ACA–A1; 6.9% hypoplastic PCA–P1; 26.5% unilateral hypoplastic PCoA; 33.3% bilateral hypoplastic PCoA |
2011 [2] |
|
|
225/cadavers |
14% complete CAC without hypoplastic arteries; 23% bilateral hypoplastic PCoA; 11.5% unilateral hypoplastic PCoA; 14% hypoplastic ACoA; 16% bilateral hypoplastic PCoA and hypoplastic ACoA |
2011 [8] |
|
|
100/CTA |
29% incomplete CAC; 43% CAC with hypoplastic artery (38% hypoplastic PCoA) |
2015 [19] |
|
|
283/CTA |
14.13% aplastic ACoA; 5.65% aplastic ACA–A1; 5.3% hypoplastic ACA–A1 |
2017 [16] |
|
|
511/CTA |
6.1% complete CAC without hypoplastic arteries; 77.5% incomplete CAC |
2021 [7] |
|
|
< 0.8 mm |
740 (544 carotid endarterectomy patients + 196 controls)/CTA |
85.5% incomplete CAC; hypoplastic artery in the anterior part of CAC in 24.5% in study group and in 41% in control group; hypoplastic artery in the posterior part of CAC in 39.3% in study group and in 32.2% in control group |
2019 [37] |
|
94/CTA |
62.8% incomplete CAC |
2019 [23] |
|
|
431/CTA and MRA |
11% invisible ACoA; 7% ACA–A1 invisible, 24% hypoplastic ACA–A1; 92% invisible PCoA; 15% invisible PCA–P1 |
2013 [29] |
|
|
< 0.5 mm PCoA and ACoA |
87/CCA |
22% aplastic ACoA; 46% aplastic PCoA sin; 41% CAC without hypoplastic arteries |
2006 [25] |
|
92/CCA |
79.3% incomplete CAC; 22.8% invisible ACoA; 1.1% hypoplastic ACoA; 43.5% invisible PCoA dex. and 5.4% hypoplastic PCoA dex.; 43.5% invisible PCoA sin. and 3.7% hypoplastic PCoA sin. |
2009 [24] |
|
|
< 0.5 mm PCoA and ACoA; < 1 mm other arteries |
100/cadavers |
25% CAC with hypoplastic arteries (11% PCA–P1, 10% PCoA; 2% ACA–A1; 2% ACoA) |
1981 [17] |
|
Diameter less than a half in comparison with the adjacent artery diameter |
50/cadavers |
4.5% CAC with aplastic PCoA (2% CAC without PCoAs bilaterally); 33/100 hypoplastic PCoA; 15/100 hypoplastic PCA–P1; 4/100 hypoplastic ACA–A1 |
2001 [1] |
|
Diameter of ACA–A1 is less than 50% of the diameter of the same contralateral artery |
204/DSA |
16.7% hypoplastic ACA–A1 in patients with ACoA aneurysm |
2017 [31] |
|
Frequency of hypoplasia (cadaveric study vs. CTA) 49.26 ± 7.28 vs. 23.69 ± 4.06; p < 0.05 |
|||
|
Frequency of aplasia (cadaveric study vs. CTA) 4.07 ± 1.41 vs. 42.07 ± 9.15; p < 0.001 |
|||
DISCUSSION
A complete and functional CAC that allows collateral blood flow has all nine vascular components in continuity and that has all vascular structures greater than 1 mm in diameter [19, 39]. It has been clinically proven that only collaterals with a diameter of at least 1 mm are effective in preventing watershed infarction [32, 35]. Arterial hypoplasia in CAC is associated with an increased risk of aneurysm formation [4, 22, 31], but also has a higher frequency in patients who have had brain ischaemia and other neurological problems [19, 23, 24, 29, 36, 37].
Almost all authors who have been interested in the morphology of CAC have shown the absolute values of the diameters of CAC arteries or CAC types made concerning the diameters of its vascular components. The analysis of published studies leads to large discrepancies in the results that may depend on the size of the sample, the analysed population [19, 23, 39], the studied pathology [7, 22, 23, 36, 37], but also on the research methodology [20]. Angiographic studies describe a lower prevalence of duplications and fenestrations [23].
Computed tomography (CT) is still a more accessible screening method than magnetic resonance imaging, especially in small hospitals or the majority of hospitals in developing countries. Although there are several generations of CT scanners, the slice thickness is usually 0.625 mm. Some CT scanners have a slice thickness of 0.6 mm or 0.5 mm. Visualization of small-sized structures on a CT image depends on the thickness of the slice, i.e. pixel characteristics, pitch factor, radiation dose, and reconstruction quality which is significantly affected by artifacts caused by surrounding structures. For all the above reasons, as well as due to contrast media injections, postprocessing techniques, and maximum intensity projection, that affect the possibilities of visualization, CTA will not be able to visualize some small diameter cerebral arteries [12, 33]. Statistical analysis of the frequency of CAC with hypoplastic and aplastic arteries in studies performed on CTA and studies performed on cadaveric material proved that CTA studies with high statistical significance more often recorded aplasia and less often hypoplasia of cerebral arteries. Precisely in this difference compared to cadaveric studies, some percentage of hypoplastic arteries remained unvisualized. Although CAC arteries less than 1 mm in diameter are considered incompetent to provide collateral blood flow in the event of obstruction of a larger supplying blood vessel, cerebral arteries can change postnatally in terms of diameter changes affected by local haemodynamics [24]. Papantchev et al. [27, 28] consider this fact but also emphasize that blood will follow the lowest resistance and pass through the arteries avoiding the hypoplastic ones. Manninen et al. [24] analysed CAC using CTA and cerebral cast angiography and discussed the possibility that arteries in CAC may enlarge in diameter due to hemodynamic shear stress in the case of ICA occlusion, while Varga et al. [37] concluded that ICA stenosis was an independent predictor of CAC morphology. In the available literature, we did not find any information about how long and to what extent a change in the calibre of arteries could be achieved, but in blood vessels of small diameter, even a small change in absolute values represents a large percentage of diameter change. This is especially important when considering the Poiseulles-Hagen law and the consequent changes in flow rate [27]. For these reasons, it is important to make a distinction between the aplasia of an artery and the impossibility of its visualization. This difference should be emphasized in publications as well as in radiological reports. Some authors consider an artery with a diameter of less than 0.8 mm as “hypoplastic/absent” [23], while others marked as hypoplastic those that are less than 1 mm in diameter or invisible on CTA and MRA [4]. Klimek-Piotrowska et al. [20] considered that CAC is complete if all its segments are despicable on CTA. Some authors analysed CAC morphology including hypoplasia, in large study series, without any defined criterion for hypoplasia [9, 13, 20, 21]. Additional misinterpretations arise when investigators try to interpret the results of cadaveric studies with data obtained from CTA studies and vice versa, without knowledge of these facts and differences. In the recent study, by trying to use a cut-off value of 0.6 mm to divide possibly invisible as a part of hypoplastic cadaveric arteries, percentages of the frequency of such blood vessels were obtained, and these percentages are very similar to the results obtained in CTA studies from the literature. Small deviations can be caused by population differences or by the fact that comparison was not done with results obtained on the same material. There is a possibility that exactly 0.6 mm is the value of the artery diameter below which the blood vessel would not be visible using CTA, but it would be interesting to perform a study on the same material using both methods and determine the cut-off value more precisely.
Karatas et al. [19] analysed CAC morphology on 100 CTA images of patients without cerebrovascular malformations and stroke, and before that, they had performed a cadaveric study. They concluded that in the CTA study complete CAC without hypoplastic arteries was recorded in 28% of cases, and including hypoplastic arteries, that percentage was 71%. In their cadaveric study, incomplete CAC was found in 9% of cases. These authors also criticized the technical limitations of the CTA method and stated that the CTA method had limitations in detecting arteries with a diameter of less than 1 mm and that CTA-detected arterial hypoplasia and aplasia should be critically analysed.
The great clinical importance of hypoplastic CAC arteries, which is described in the literature, leads first to the need for a clear definition of the term hypoplasia, and then for a precise determination of the technical limitations of visualization radiological methods used in daily clinical practice.
Several authors emphasize that it is necessary to radiologically observe and especially describe the morphology of CAC not only when examining the brain, but also during other examinations such as imaging the blood vessels of the neck [7] or when preparing for interventions on the arch of the aorta [27, 28].
Limitations of the study
Studies performed using CTA show the diameter of the arterial lumen because they visualize the contrast agent within the lumen, while studies on cadaveric material show the outer diameter of the blood vessel that can be more or less collapsed because of the lack of circulation. In elderly people, atherosclerotic plaques can contribute to the reduction of blood vessel diameter values on CTA and their increase in cadaveric studies. There is still no data on possible post-mortem changes (during the first 24 hours) in the wall of brain arteries, which could lead to false measurement changes in blood vessel diameter during autopsies, also. The authors believe that the stated reasons are the cause of the differences in absolute arterial measurement values, but there is a possibility that they should not be the cause of statistically significant differences, especially in studies of a large number of cases.
CONCLUSIONS
Arteries larger than 1 mm in diameter existed in 15.2% of the examined CACs, and among that communicating arteries had the highest frequency of hypoplastic form. If a value of 0.6 mm were used as a cut-off, below which CTA could not visualize the artery, aplasia of one of the vascular components would most likely be recorded by CTA in 30.6%, while it existed in 5.1% of cases. These results approximate data from CTA studies in the literature. Comparison of literature data and the finding of statistically significant differences in the prevalence of hypoplastic and aplastic arteries in CTA and cadaveric studies indicate significant technical limitations of CTA in the visualization of arteries of small diameter.
We suggest that hypoplastic arteries should be with a diameter of less than 1 mm because, below that value, an artery is not capable to provide collateral circulation in CAC. There is a high probability that arteries with a diameter of less than 0.6 mm are invisible on CTA.
ARTICLE INFORMATION AND DECLARATIONS
Ethics statement
The authors state that every effort was made to follow all local and international ethical guidelines and laws that pertain to the use of human cadaveric donors in anatomical research [15] while conducting this study.
The approval for research is obtained from the Research Ethics Committee (No. 01-9068-4) of the Faculty of Medicine University of Niš.
Acknowledgments
This study was funded by the Ministry of Science, Technological Development and Innovation of Republic of Serbia (Grant No: 451-03-47/2023-01/200113), Internal project of Faculty of Medicine, University of Niš (No. 38/20), and the Slovenian Research Agency (P3-0293 research program).
Autopsied donors and their families deserve our highest gratitude.
Conflict of interest
None declared.
