Blood Flow in Circle of Willis Review Pape

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Peer-reviewed

Research Article

Variations in the Circumvolve of Willis in a large population sample using 3D TOF angiography: The Tromsø Report

• Lars B. Hindenes,
• Asta K. Håberg,
• Liv Hege Johnsen,
• Ellisiv B. Mathiesen,
• David Robben,
• Torgil R. Vangberg

x

• Published: November 3, 2020
• https://doi.org/x.1371/journal.pone.0241373

Figures

Abstract

The main arteries that supply blood to the brain originate from the Circumvolve of Willis (CoW). The CoW exhibits considerable anatomical variations which may have clinical importance, merely the variability is insufficiently characterised in the general population. We assessed the anatomical variability of Cow variants in a customs-dwelling sample (Northward = 1,864, 874 men, hateful age = 65.4, range 40–87 years), and independent and conditional frequencies of the CoW'south avenue segments. Moo-cow segments were classified as nowadays or missing/hypoplastic (w/1mm diameter threshold) on 3T time-of-flight magnetic resonance angiography images. We as well examined whether age and sex were associated with Cow variants. We identified 47 unique Moo-cow variants, of which five variants constituted 68.v% of the sample. The complete variant was found in xi.ix% of the subjects, and the well-nigh common variant (27.8%) was missing both posterior communicating arteries. Conditional frequencies showed patterns of interdependence across most missing segments in the Moo-cow. Cow variants were associated with hateful-split historic period (P = .0147), and at that place was a trend showing more missing segments with increasing age. We found no association with sex (P = .0526). Our population report demonstrated historic period as associated with CoW variants, suggesting reduced collateral capacity with older age.

Citation: Hindenes LB, Håberg AK, Johnsen LH, Mathiesen EB, Robben D, Vangberg TR (2020) Variations in the Circle of Willis in a big population sample using 3D TOF angiography: The Tromsø Study. PLoS ONE xv(eleven): e0241373. https://doi.org/10.1371/journal.pone.0241373

Editor: Pascal A. T. Baltzer, Medical University of Vienna, Republic of austria

Received: July 3, 2020; Accustomed: Oct fourteen, 2020; Published: November 3, 2020

Copyright: © 2020 Hindenes et al. This is an open up access article distributed nether the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original writer and source are credited.

Data Availability: Ethical and legal restrictions prohibit the authors from making the dataset available outside The Tromsø Report database, which is available by contacting The Tromsø Study. Please see https://en.uit.no/forskning/forskningsgrupper/sub?p_document_id=453582&sub_id=669706 for detail on how to obtain access to all relevant data.

Funding: This work was supported by a Helse Nord project grant (HNF1369-17) to LBH and (SFP1271-xvi) for collecting the MR data. Icometrix provided salary for DR. Helse Nord and Icometrix had no role in study design, data collection and analysis, decision to publish, or grooming of the manuscript. The specific roles of these authors are articulated in the 'author contributions' section.

Competing interests: The authors declare no disharmonize of interests. DR received salary from Icometrix during this study, but this does non alter our adherence to PLOS ONE policies on sharing data and materials.

Introduction

The main blood supply to the brain originates from the left and correct internal carotid arteries and the basilar artery. These arteries anastomose to course the Circle of Willis (CoW) at the base of the brain (S1 Fig in S1 File). The round arrangement of the arteries enables the redistribution of blood flow when arteries in or upstream of the CoW experience reduced flow. This collateral power of the CoW provides redundancy in the blood supply to the brain. Segments in the Cow are commonly missing or hypoplastic rendering the CoW incomplete, thereby reducing the collateral capacity of the CoW and increasing the encephalon'due south vulnerability to changes in the blood flow [ane–3].

The CoW anatomy is clinically relevant as incomplete CoW variants are associated with an increased risk of cerebrovascular disease. Studies on patient samples find that incomplete Cow variants are associated with stroke [4, five], aneurisms [6, 7] and white matter hyperintensities [8–11]. The CoW variants are also important in certain surgical procedures [12, xiii]. It is not clear if incomplete variants pose a similar risk in the general population.

Greatly varying prevalence estimates limit our understanding of the anatomical variability in the Moo-cow. For example, the estimated prevalence of the complete variant range from 12.2% [3] to 45.0% [xiv]. Differences in sample characteristic [1, 12, 15, 16], sample size [17], and measuring techniques [1, xv] are sources of variability. Additionally, many Moo-cow classification schemes cannot be compared fully, complicating the comparing betwixt studies [ane, 11, 18–xx]. Common classification schemes include using 1 or more diameter thresholds for arteries [5, 12, 18, xix, 21, 22], comparing diameters of arteries relative to other arteries' diameter [three, 6, 23], or a mix of both [1, 8, 15, 24]. Other schemes dissever the CoW classification into anterior and posterior circulation [ane, five], or omit distinguishing betwixt left and right sided variants [two, iii, twenty]. I study did non report its nomenclature scheme [2].

The primary goal of this study was to report population-based estimates of the prevalence of CoW variants based on 3T MR angiography images using a classification scheme adapted for more detailed quantitative analyses. We also examined if CoW variants were associated with age and sex activity, and we reported the frequency of private missing arteries in the CoW and similarly their conditional frequencies, independently of Cow variants.

Materials and methods

The Tromsø Study

The Tromsø Study is a population-based cohort study recruiting from the Tromsø municipality in Norway. This study has been performed every six to vii years since 1974 and the seventh survey (Tromsø 7) was performed in 2015–2016. Tromsø vii consisted of two visits. All inhabitants to a higher place age 40 were invited to the 1^st visit, and 20,183 subjects participated (65% participation charge per unit). A subset of participants in the get-go office of the Tromsø 7 Study were invited to a two^nd visit, where 8,346 subjects participated. Of these, 2,973 were invited to partake in a cantankerous-sectional magnetic resonance (MR) study. Of the invited, 525 declined, 396 did not respond, 169 had conditions prohibiting MR examinations, and five had moved or were dead. Furthermore, for xiv cases we were unable to find at to the lowest degree one of three baseline MRI series, consequently yielding ane,864 subjects with fourth dimension-of-flight (TOF) angiography serial, T1-weighted series, and T2-weighted fluid-attenuated inversion recovery (FLAIR) series (Fig ane). The study was canonical by the Regional Committee of Medical and Health Inquiry Ethics Northern Norway (2014/1665/REK-Nord) and carried out in accordance with relevant guidelines and regulations at UiT The Arctic University of Norway. All participants gave written informed consent before participating in the written report.

Fig 1. Flow chart of the selection of subjects from the seventh Tromsø Study to the current report.

MR = Magnetic resonance, MRI = Magnetic resonance imaging, TOF = Time-of-flight angiography series, T1 = T1-weighted series, FLAIR = T2-weighted fluid-adulterate inversion recovery series.

https://doi.org/x.1371/periodical.pone.0241373.g001

MRI protocol

Participants were scanned at the University Hospital North Norway in a 3T Siemens Skyra MR scanner (Siemens Healthcare, Erlangen, Germany). A 64-aqueduct head coil was used in nearly examinations, but in 39 examinations, a slightly larger xx-channel head coil had to be used. The MRI protocol consisted of a 3D T1-weighted serial, a 3D T2-weighted FLAIR serial, a susceptibility weighted series and a TOF angiography series, with a full scan time of 22 minutes. Only the TOF images were used in this report. These were caused with a 3D transversal fast low angle shot sequence with flow compensation (TR/TE = 21/3.43 ms, parallel imaging acceleration factor iii, FOV 200 × 181 mm, slice thickness 0.five mm, 7 slabs with 40 slices each). Reconstructed image resolution was 0.3 × 0.three × 0.5 mm. The slice prescription was automatically aligned to a standardized brain atlas ensuring consistency across examinations [25].

Classification of CoW variants

TOF images were evaluated by LBH, using a program created in MeVisLab (v3.0.1). The program displays the TOF images both every bit a 3D rendering or a maximum intensity projection (MIP), and in 2D with a lumen diameter measurement tool. For rating an avenue as present, the following criteria were used: (1) visible forth its entire segment on the 3D rendering, (ii) have a diameter larger than 1 mm, (3) connected to other arteries as in the complete textbook Moo-cow. It is hard to reliably identify smaller than i mm on TOF MRI due to the paradigm resolution and possibly depression menstruation rates in minor arteries. Due to these limitations, nosotros followed the convention as in most studies of the CoW [1, 5, 12, xviii, 19, 21, 22] and did not differentiate betwixt missing and hypoplastic segments. Nosotros emphasize, yet, that when we refer to missing segments of the Cow nosotros mean "missing or hypoplastic". The nomenclature criteria are illustrated in Fig 2 with different degrees of hypoplastic/missing arteries. Compare it to S1 Fig in S1 File for a complete "textbook-type" Cow.

Fig 2. 3D volume rendering of a time-of-flying image depicting three classification cases inside our classification scheme.

Green arrow: The right anterior cerebral artery is present. Yellow arrow: The left posterior cerebral artery is hypoplastic or missing, and simply beneath 1mm in bore. Red arrow: The right posterior cerebral artery is clearly missing. The configuration itself is of bilateral missing posterior cognitive avenue (2P) blazon. Image follows neurological convention, where left is left and correct is right. An orientation cube in the lower correct corner bear witness orientation, and its P denotes posterior.

https://doi.org/10.1371/periodical.pone.0241373.g002

The CoW consists of seven arteries, all of which were considered in our variants. Starting time, the left and right proximal anterior cerebral artery (ACA), the inductive communicating artery (ACoA), the left and right posterior communicating artery (PCoA), and the left and right proximal posterior cerebral avenue (PCA). We too considered the three largest in-menstruation arteries, both the left and right internal carotid artery (ICA) and the basilar artery (BA), and the left and correct middle cognitive artery (MCA) in relation to the variants, because they, although rarely, can be missing and are important for interpreting the collateral flow in a CoW. The distal ACA and distal PCA segments were not considered since they are about always present and can receive collateral flow through ACoA, and PCoA or PCA, respectively. A textbook CoW is visualised in S1 Fig in S1 File. There were some rare variants that did not fit into the regular classification of the Cow, such as the persistent archaic trigeminal artery, described in Dimmick et al. [26], which was ignored. Arterial segments that did non connect to their expected locations were classified co-ordinate to the third benchmark. For instance, variations in the ACoA, of which in that location are many of [three], were all regarded equally a single ACoA. Furthermore, a posterior CoW variant named unilateral dual PCA (S2 Fig in S1 File) was categorized every bit missing a PCoA using the tertiary criterion, because of the missing connection between the PCoA and its ipsilateral PCA. This simplification via the 3rd criterion does not compromise the descriptions of the collateral menses ability inside each Cow variant.

We labelled the CoW variants using a classification similar to previous studies [1, 6], where each variant's name signified the missing segments. For brevity, ACA were denoted by "A", ACoA past "Ac", PCA by "P", PCoA by "Pc", ICA by "I", MCA by "M", and BA past "B". Alternatively, when no artery segment was missing a complete CoW was denoted by "O". To specify whether a missing segment was in the left or correct hemisphere, an "l" or "r" suffix is used. If the same segment was missing on both sides the number "2" was instead used every bit a prefix, eastward.yard. "2Pc" for the variant where both PCoA are missing. This scheme ensured unique names for all Moo-cow variants. Run into Fig 3 for illustrations of variants with their corresponding label.

Fig 3. Complete graphical overview of all Circle of Willis variants observed in the current study.

All variants are sorted get-go by (descending) frequency and and so, in case of equal frequencies, past alphanumerical ordering. Each variant's name is put together by the missing segments with the following notation: O = Complete variant (no missing arteries), Air-conditioning = Anterior communicating artery, A = Anterior cognitive avenue, Pc = Posterior communicating artery, P = Posterior cognitive artery, I = Internal carotid artery, Yard = Middle cerebral artery, B = Basilar artery, while the suffixes "r" and "50" announce correct and left lateralization of arteries. The prefix "2" denotes bilateral missing arteries.

https://doi.org/10.1371/journal.pone.0241373.g003

A random sample (N = 100) was blinded and reclassified by the aforementioned rater (LBH), and likewise another rater (TRV) blinded to the original nomenclature, in gild to measure intra- and inter rater accurateness.

Comparing with other studies

To contextualise our Moo-cow variant frequencies, we wanted to compare with other studies. Unfortunately, to our knowledge, there is merely one other Cow TOF MR written report with a like sample size compared to ours. The study is in 2246 salubrious Chinese men [3], and we were able to perform comparisons with their report with only modest adaptations of the nomenclature of the CoW variants. Master changes included removing left and correct lateralization in our Moo-cow variants, and translating their CoW variants to our nomenclature. Further information about the comparing is constitute in the S1 and S2 Files.

Statistical analysis

We split the Cow data at hateful age of participants, grouping subjects into a "younger" and "older" group (Tabular array 1). We also grouped the subjects into age per decade (5 categories, 40 years to 90 years). Formulas used to calculate all frequencies for every CoW segment and variant are described in the S1 File. CoW variants observed less than ten times were grouped into a single composite category of rare variants (S1 Tabular array in S1 File). This blended category was created to include all subjects when testing without having too few observations in the assortment elements (run into S1 File for details). The Cochran-Mantel-Haenszel test was used to test whether CoW variant frequencies were associated with sexual practice, and age. This test allows for testing provisional independence betwixt 2 factors while controlling for a third cistron. As such, we used the Cochran-Mantel-Haenszel test to test for conditional independence between CoW variants and sex activity while decision-making for the dichotomic age variable, and to test for conditional independence between Moo-cow variants and dichotomic age while controlling for sex. Both of these tests had array dimensions 23 × 2 × ii. The outcome of historic period was further examined by plotting the distribution of CoW variants for each decade. To assess whether sexual practice might affect this plot, a 5 × 2 Chi-squared test betwixt age per decade and sexual activity was performed to assess independence (Table ane). We considered a Bonferroni corrected P < 0.05 as significant (nominal P < 0.0167). At terminal, the accuracy metric was used to appraise the intra- and inter rater validation. All computations were performed in R (v3.four.four) and three figures were created using the ggplot2 package [27].

Results

Study participants

The mean historic period for all participants was 65.4 years (SD = 10.half dozen). In that location were 874 men (47%), mean age 66.1 years (SD = 10.4, range = 40–86 years), and 990 women (53%), mean age 64.7 years (SD = 10.7, range = 41–87 years). Distributions of both mean-split age and decade age groupings with respect to sex are shown in Table 1, and distribution of age for men and women are shown in S3 Fig in S1 File.

Frequencies of Cow variants

Nosotros found 47 unique variants of the Cow (Fig three). Of these, 22 made up 96.viii% of the sample (Table 2), while the remaining 25 variants had less than x observations each and constituted in total only 3.2% of the sample (S1 Table in S1 File). The most mutual variants were, 2Pc (27.viii%), with both PCoA segments missing, Pcl (12.2%), with the left PCoA segment missing, the complete O variant (eleven.9%), Ac2Pc (9.3%), with the ACoA and both PCoA missing, and Pcr (seven.3%) with the right PCoA missing. These five about mutual CoW variants constituted 68.v% of the full sample. These findings suggest that just about 12% of the adult population accept a complete Cow, while the remaining 88% have one or more missing segments, thus reducing their collateral chapters.

Table ii. Frequencies of mutual Circle of Willis variants for the whole sample, and their frequencies for men and women, and for existence below and to a higher place mean age [number of cases (per centum of column total)].

https://doi.org/10.1371/journal.pone.0241373.t002

Comparison of adapted CoW estimates with a previous written report

After adapting the Moo-cow estimates, nosotros were able to compare 18 of our resulting prevalence estimates to the well-powered Chinese study [iii] (S1 and S2 Files). This comparing showed excellent agreement; with mean and median pct point differences of ane.6 and 0.8 respectively (range 0.1–x.half-dozen percent points). The difference between the consummate variant estimates was merely 0.iii percentage points. About of the total 28.iv pct point difference could be attributed to variants missing PCoA or PCA. In the end, nosotros compared 99.2% of our sample with 100% of the other study, resulting in only an boosted 0.8 percent point bias. In sum, the comparison showed near-perfect agreement for nearly all Moo-cow variants.

Frequencies of missing segments independent of CoW variant

The frequencies of missing Moo-cow segments in the whole sample are shown in Fig iv. The left and correct PCoA were most frequently missing (sixty.6% and 53.6%), followed by the ACoA (22.7%). In that location was a notable correct-left disproportion in the frequencies of missing ACA and PCoA, but not for PCA. The correct-to-left ratio for ACAs (4.3%/1.viii%) was large, considering how infrequent the ACAs were missing.

Fig 4. Frequency that each artery is missing independently of Circle of Willis variants and other arteries.

Nominators and denominators are in respective parentheses, and represent respectively the number of times an artery is missing and the full number of subjects. ACA: Anterior cerebral artery. ACoA: Anterior communicating artery. PCoA: Posterior communicating avenue. PCA: Posterior cognitive avenue. ICA: Internal carotid artery. MCA: Heart cerebral Artery. BA: Basilar artery. Hemispheric left and right lateralization are denoted by "L" and "R" respectively.

https://doi.org/10.1371/journal.pone.0241373.g004

Pairwise conditional frequencies of missing segments

The heatmap of provisional frequencies (Fig v) shows the provisional probabilities between Moo-cow segments that were commonly missing, i.e. PCoA, PCA, ACA and ACoA (Fig 4). Although the provisional frequencies ultimately reverberate the observed variant frequencies, the heatmap representation reveals several interesting patterns. First, ACoA was seldom missing if the left or correct ACA was missing. Second, each ACA, PCoA and PCA segment pairs had approximately equal probability of being missing if the ACoA was missing. Third, if ACA was missing on one side, it was much more than likely that the PCA was missing on the same side than on the opposite side, suggesting an ipsilateral pattern. Fourth, a contralateral pattern existed between ACA and PCoA, i.eastward., if the ACA was missing on ane side, it was more likely that the PCoA was missing on the other side. Lastly, similar contralateral patterns were besides seen between PCA and PCoA, inside the PCoA pair, and within the PCA pair.

Fig 5. Heatmap of conditional probabilities that Y-artery is missing given that X-artery was missing.

Numerators and denominators of conditional probability estimates are provided in the brackets, and represent respectively the number of times two segments are missing at the same fourth dimension (joint probability) and per column the number of times the artery X is missing (independent probability). The common denominator of the joint probabilities and independent probabilities have cancelled. ACA: Anterior cerebral artery. ACoA: Anterior communicating avenue. PCoA: Posterior communicating artery. PCA: Posterior cerebral artery. Left and right lateralization are denoted past "Fifty" and "R" respectively. Each successive heatmap interval increases in size with 0.05.

https://doi.org/10.1371/periodical.pone.0241373.g005

Tests of provisional independence betwixt Moo-cow variant frequencies and sexual practice, and age, while controlling for the other

The Cochran-Mantel-Haenszel test of conditional independence between sex and CoW variant frequencies while controlling for historic period (Table ii), resulted in Thouⁱⁱ(22, North = one,864) = 33.702 with unadjusted P = .0526. This event imply that sex is not significantly associated with the frequency of Moo-cow variants when corrected for hateful split age.

The second Cochran-Mantel-Haenszel exam (Tabular array 2) tested whether Cow variant frequencies were conditionally independent of being higher up or below sample mean historic period while controlling for sexual practice. This test returned M²(22, Due north = 1,864) = 38.849 with unadjusted P = .0147, demonstrating that the mean-split age group was associated with the distribution of CoW variants, when corrected for sex.

CoW variant frequencies per decade

Fig 6 shows Moo-cow variant frequencies per decade. From this figure, nosotros observed that for each increasing decade the Moo-cow variants that were missing a single avenue (Air-conditioning, Pcl and Pcr) and the complete variant became less common. We besides observed that the blended category of rare Cow variants became more than mutual in later decades. These observations suggest that information technology is more common in older age to have more than missing segments in the CoW.

Fig 6. Stacked bar plot of the frequencies of the about common Circle of Willis variants divided into age intervals as decades.

Each variant is put together by the missing segments with the following annotation: 2P: Missing bilateral posterior cerebral artery. 2Pc: Missing bilateral posterior communicating artery. Ac: Missing anterior communicating avenue. Pc: Missing posterior communicating artery. P: Missing proximal posterior cerebral artery. A: Missing proximal anterior cerebral artery. Left and right lateralization are denoted by using "l" or "r" respectively equally a suffix for eligible segments. Special cases exempt from the preceding are: O: Complete variant, i.e. no missing segments. Rare/Other: Composite category of other rare variants with ane or more missing segments.

https://doi.org/x.1371/journal.pone.0241373.g006

Examination of independence between sexual practice and decade historic period groups

The 5 × 2 Chi-squared test was carried out (Tabular array 1) to exam for independence betwixt the sexual practice and age as decades group in Fig 6. This test yielded 10²(4, N = 1,864) = 8.482 with unadjusted P = .075, implying homogeneous distribution of men and women beyond the 5 decades. Thus, due to the homogeneity result, Fig half dozen is statistically appropriate to interpret equally for both sexes.

Intra- and inter rater validation

The intra rater validation yielded an accuracy score of 79% (alien nomenclature in 21 of 100 cases). Closer inspection showed that but a unmarried artery was mismatched for all 21 variant mismatches (S4 Fig in S1 File). The ACoA was prone to ambiguity with a total of 12 mismatches. ACA and PCA were misclassified as present instead of missing in four and 3 cases, respectively.

The inter rater validation yielded an accuracy score of 82% (conflicting nomenclature in xviii of 100 cases). Compared to the intra rater validation, the inter rater validation had higher accuracy score, but had on the opposite more severe misclassifications. In other words, the mismatches were not only single artery mismatches. See S5 Fig in S1 File for details on the inter rater validation.

Word

This is, to our noesis, the largest population-based study on the anatomical variation of the CoW, that included both men and women. The large sample size and recruitment of participants from the general population provide prevalence estimates of the anatomical variation in the Moo-cow co-ordinate to our classification scheme for people between xl to ninety years of age. Principal findings were that only 11.9% had a complete textbook Cow variant, while the remaining 88.i% had one or more missing segments in the CoW. In total, we constitute 47 variants of the Cow, but only v of these variants were very mutual (i.due east. nowadays in > 5%). Further notable findings were that Moo-cow frequencies were associated with age, but not with sex, and that in that location were patterns of interdependent missing segment patterns across Cow variants.

The agreement in prevalence estimates between our study and a comparable well-powered written report [three] has several possible implications. First, the similarities betwixt a male Chinese population and a Norwegian population suggest that variations in the Moo-cow are similar across populations. A notion consequent with a study on twins finding no genetic effect on the variability of the Cow [14]. 2nd, it supports our finding that sex activity is non associated with the anatomical variability in the CoW, since the study past Qiu et al. [3] only included men, while our study included both women and men in an approximately equal proportion. Third, since most previous studies have relied on sample sizes of upwards to a few hundred participants, it is likely, considering the understanding betwixt two studies with a sample size of about 2000, that the disagreement between prevalence estimates in previous studies stems from too modest study samples.

We constitute that Cow frequencies were associated with historic period, which has been observed in other studies [1, 22, 28]. These studies institute, similarly to our study, that the number of missing arteries increased with age. Although the underlying cause of the increment in missing segments with age is not clear, atherosclerosis has been suggested as a possible cause [22], since plaque in an arterial segment might reduce the menses so that the segment is non detected on period-sensitive TOF MRI. The reduction in cognitive blood catamenia with historic period [29] perhaps in conjunction to the increase in tortuosity of claret vessels with historic period [30] could as well alter the flow pattern in the CoW such that in that location is no, or very little menses in some segments, which would as well announced as missing segments in the Cow. It is therefore non incommunicable that the increased rate of missing segments with historic period is caused by atherosclerosis or other factors affecting the claret flow in the Cow.

Nosotros did not find an association betwixt sex and the frequencies of Cow variants. Previous studies take reported conflicting findings regarding the effect of sex activity; some find that the consummate variant is more prevalent in women [one, 28], that specific variations are more mutual in men or women [6], or that at that place is no clan [22]. Differences in methods, sample sizes and statistics, make it difficult to compare our results to the previous findings. Withal, the large sample size and correction for a possible age bias in our analysis, suggest that the outcome of sex activity on the anatomy of the Moo-cow is not substantial.

Report limitations were as follows. Outset, the TOF MR technique is sensitive to blood menstruation, i.e. it is necessary for blood to menstruum with a sufficient speed to be visible on the TOF images. As such nosotros are only visualising blood flow, not arteries, and some of the missing CoW vessels might well be present, but not visible on the TOF images. This is supported by the higher frequency of the complete CoW variant in autopsy studies [31, 32], but information technology is worth noting that autopsy studies also show that some sections in the Cow tin can be completely absent besides [31]. Second, we did non differentiate between missing and hypoplastic segments. Although this is washed in nigh CoW studies [ane, five, 12, eighteen, 19, 21, 22], our prevalences exercise not reverberate all the nuances in the CoW. There is also a functional stardom between missing and hypoplastic segments every bit hypoplastic segment may provide some collateral catamenia, which is overlooked with our classification. 3rd, as seen from the intra- and inter rater validation there were some misclassifications in ambiguous cases of certain arteries. In detail, the ACoA was associated with higher rate of misclassification than other arteries. Some cases of ACA, PCoA and PCA were also mismatched, simply not of the same magnitude as ACoA. Every bit such, estimates including ACoA should exist considered less authentic. Last, because of the large number of variants found, the precision of frequencies for a given variant should exist judged relatively to its number of observations. On the other manus, our report strengths were equally follows: (one) a large sample size, (2) a rigorous and reproducible classification scheme, and (3) intra- and inter rater validation indicating similar classification robustness beyond each rater.

In decision, in a large population sample, 47 anatomical variants of the Cow were plant, but only 5 variants were normally encountered. The complete Cow variant was the third near frequent variant present in 11.9% of the sample. Hateful-carve up historic period was significantly associated with CoW variant frequencies, which could exist partially explained by the increased number of hypoplastic or missing arteries with increasing age. We also found interdependent hypoplastic or missing segment patterns betwixt the ACAs, ACoA, PCoAs, and the PCAs, highlighting the importance of too including the whole CoW during assessment to retain information about the Cow variants' collateral ability. Our variant frequencies agreed well with another large-scale MRI study in Chinese men suggesting the possibility of similar CoW variant frequencies across different populations, and that large variability in Moo-cow variant frequency in the literature possibly stems from using too small samples. The observed increasing number of hypoplastic or missing segments with historic period suggests that the collateral power of the Cow may go an increasingly important take a chance factor for encephalon health with older age.

Supporting information

Acknowledgments

Nosotros warmly give thanks the participants of the Tromsø Report, the assistants of the Tromsø Study, the Department of Radiology at the Academy Hospital N Norway and the MR imaging technologists for their contributions to the report.

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