MRI-Based Definition of a Stereotactic Two-Dimensional Template of the Human Insula

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Fax +41 61 306 12 34 E-Mail [email protected] www.karger.com Laboratory Investigation Stereotact Funct Neurosurg 2009;87:385–394 DOI: 10.1159/000258079 MRI-Based Definition of a Stereotactic Two-Dimensional Template of the Human Insula Afif Afif a, b Dominique Hoffmann c Guillaume Becq d Marc Guenot a Michel Magnin e Patrick Mertens a, b a Department of Neurosurgery, Neurological Hospital, Hospices civils de Lyon, and b Department of Anatomy, Inserm U 879, Lyon 1 University, Lyon, c Department of Neurosurgery, Grenoble University Hospital, and d Laboratory of Epilepsy, Grenoble University Hospital, Grenoble, and e INSERM, U 879, Bron, France to the classical AC-PC stereotactic reference system. They furthermore allow us to quantify the probability that a given element of this structure is located at a predefined position. This should be useful in functional neuroimaging studies and in insular surgery for diagnostic and therapeutic goals. Copyright © 2009 S. Karger AG, Basel Introduction The first rough sketch of the insula by Vesalius dates from more than four centuries ago [1]. However, only at the end of the 19th century did authors produce detailed qualitative descriptions of this peculiar part of the cere- bral cortex, also called at that time ‘the island of Reil’ [1–5]. In his comparative anatomical study, Clark [3] em- phasized the marked interhemispheric variations that af- fect the insula’s intrinsic morphology. Since then, few quantitative studies on the topographic anatomy of the insula have been published, the exception being the work by Türe et al. [6] on formalin-fixed human brains. This paucity of information may result from the difficulty in accessing this structure. The insula rests deep in the syl- vian fissure, hidden by the other cerebral lobes behind the temporoparietofrontal opercula. In addition, the syl- Key Words Cerebral magnetic resonance imaging Insula Morphometry Neurosurgery Stereotaxy Abstract Objective: This study aimed to create a stereotactic two-di- mensional description of the human insula based on accu- rate radiological morphometric studies. Methods: Seventy- five normal cerebral MRIs were selected and drawings of the insula then obtained from serial sagittal slices. These draw- ings were digitalized before superimposing the anterior (AC) and posterior (PC) commissures as references. This allowed us to quantify interindividual anatomical variations in a large cohort of subjects. Results: The morphometric analysis of the insula revealed a more complex shape than previously described. This structure is delimited by four peri-insular sul- ci (anterior, superior, posterior and inferior) instead of the three sulci classically mentioned. Males have a statistically larger surface area than females, according to a correlated index. Precise measurements of the different insular compo- nents allowed us to quantify their potential interindividual anatomical variations and to define their average shapes and stereotactic locations. Conclusion: These data create a two-dimensional template of the human insula, with regard Received: October 2, 2008 Accepted after revision: March 25, 2009 Published online: November 12, 2009 Afif Afif, MD, PhD Department of Anatomy, Lyon 1 University 8, avenue Rockefeller FR–69003 Lyon (France) Tel. +33 4 78 77 71 43, Fax +33 4 78 77 71 74, E-Mail [email protected] © 2009 S. Karger AG, Basel 1011–6125/09/0876–0385$26.00/0 Accessible online at: www.karger.com/sfn

Transcript of MRI-Based Definition of a Stereotactic Two-Dimensional Template of the Human Insula

Fax +41 61 306 12 34E-Mail [email protected]

Laboratory Investigation

Stereotact Funct Neurosurg 2009;87:385–394 DOI: 10.1159/000258079

MRI-Based Definition of a Stereotactic Two-Dimensional Template of the Human Insula

Afif Afif a, b Dominique Hoffmann c Guillaume Becq d Marc Guenot a

Michel Magnin e Patrick Mertens a, b

a Department of Neurosurgery, Neurological Hospital, Hospices civils de Lyon, and b Department of Anatomy, Inserm U 879, Lyon 1 University, Lyon , c Department of Neurosurgery, Grenoble University Hospital,and d Laboratory of Epilepsy, Grenoble University Hospital, Grenoble , and e INSERM, U 879, Bron , France

to the classical AC-PC stereotactic reference system. They furthermore allow us to quantify the probability that a given element of this structure is located at a predefined position. This should be useful in functional neuroimaging studies and in insular surgery for diagnostic and therapeutic goals.

Copyright © 2009 S. Karger AG, Basel

Introduction

The first rough sketch of the insula by Vesalius dates from more than four centuries ago [1] . However, only at the end of the 19th century did authors produce detailed qualitative descriptions of this peculiar part of the cere-bral cortex, also called at that time ‘the island of Reil’ [1–5] . In his comparative anatomical study, Clark [3] em-phasized the marked interhemispheric variations that af-fect the insula’s intrinsic morphology. Since then, few quantitative studies on the topographic anatomy of the insula have been published, the exception being the work by Türe et al. [6] on formalin-fixed human brains. This paucity of information may result from the difficulty in accessing this structure. The insula rests deep in the syl-vian fissure, hidden by the other cerebral lobes behind the temporoparietofrontal opercula. In addition, the syl-

Key Words

Cerebral magnetic resonance imaging � Insula � Morphometry � Neurosurgery � Stereotaxy

Abstract

Objective: This study aimed to create a stereotactic two-di-mensional description of the human insula based on accu-rate radiological morphometric studies. Methods: Seventy-five normal cerebral MRIs were selected and drawings of the insula then obtained from serial sagittal slices. These draw-ings were digitalized before superimposing the anterior (AC) and posterior (PC) commissures as references. This allowed us to quantify interindividual anatomical variations in a large cohort of subjects. Results: The morphometric analysis of the insula revealed a more complex shape than previously described. This structure is delimited by four peri-insular sul-ci (anterior, superior, posterior and inferior) instead of the three sulci classically mentioned. Males have a statistically larger surface area than females, according to a correlated index. Precise measurements of the different insular compo-nents allowed us to quantify their potential interindividual anatomical variations and to define their average shapes and stereotactic locations. Conclusion: These data create a two-dimensional template of the human insula, with regard

Received: October 2, 2008 Accepted after revision: March 25, 2009 Published online: November 12, 2009

Afif Afif, MD, PhD Department of Anatomy, Lyon 1 University 8, avenue Rockefeller FR–69003 Lyon (France) Tel. +33 4 78 77 71 43, Fax +33 4 78 77 71 74, E-Mail [email protected]

© 2009 S. Karger AG, Basel1011–6125/09/0876–0385$26.00/0

Accessible online at:www.karger.com/sfn

KNECHTE
hoch

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vian veins and middle cerebral artery collaterals form a complex and dense arteriovenous vascular network on its lateral surface [7–10] .

Talairach’s [11, 12] cerebral atlas defines the insular lobe as a triangle referred to the anterior commissural-posterior commissural (AC-PC) baseline, without fur-ther detail. More recently, researchers have used three-dimensional reconstruction of the human brain to spec-ify sulcal and gyral patterns of the cerebral cortex [13–22] . However, these studies do not detail the sulcal and gyral patterns of the insular lobe.

Moreover, studies using functional imaging tech-niques (fMRI and PET) [23–25] , direct intracerebral elec-trical stimulation [13, 26–29] , and tract-tracing [30] sug-gest an important functional role for the insular cortex in producing language and processing grammar [31–34] , pain [25, 31, 35–39] , cardiovascular regulation [27, 40] , auditory processing [33, 41, 42] , and visceral sensorimo-tor phenomena [28, 33] .

However, these different functions have not been lo-calized accurately within the human insular cortex with respect to the sulcal and gyral patterns of this structure.

This study aimed to create a two-dimensional tem-plate of the insular lobe in the stereotactic AC-PC refer-ence system. This work should help localize this deep cortical region and its gyral subdivisions on MRI.

Materials and Methods

Subjects The cerebral MRIs from 115 patients undergoing stereotactic

neurosurgery were reviewed. Among them, those from 52 pa-tients suffering from epilepsy of insular origin and/or presenting with anatomical abnormalities (malformations, cavernoma or at-rophy) within the insular or adjacent regions were rejected. Thus, only the MRIs from 63 patients (age: 5–53 years; mean: 27.68 years; 95% confidence interval, CI: 24.84–30.51 years) with visu-ally normal insular regions were included. Among these 63 pa-tients, parasagittal MRIs were only available for 75 hemispheres (38 right and 37 left), of which 42 were of male origin (56%) and 33 were from a female (44%). Images of both right and left hemi-spheres were only available for 12 patients. All patients suffering from severe, drug-refractory partial epilepsy were investigated by stereo-electroencephalography at the University Hospital of Grenoble (France) to evaluate the precise location of their epilep-togenic zone. Cerebral contrast T 1 -MRI scans were obtained un-der stereotactic conditions. Imaging parameters included echo spin, repetition time (TR) = 500 ms, echo time (TE) = 10 ms, sec-tion thickness = 4 mm, and intersection gap = 1 mm.

Data Acquisition Individual drawings of the insula were built up based on se-

rial parasagittal slices (4 mm thick) from each cerebral MRI. Both

the AC and PC were identified on the midline sagittal slice. A line passing through the superior edge of the AC and the inferior edge of the PC was then drawn, as well as vertical lines orthogonal to the AC-PC line, one tangential to the posterior edge of the AC (VAC), the other tangential to the anterior edge of the PC (VPC). These landmarks defined an individual bicommissural reference system [43] . The reconstruction started at the midline and pro-gressed to the lateral surface of the hemispheres, on a one-to-one scale ( fig. 1 ). The reconstruction of each individual insular lobe was made by tracing every peri-insular and insular sulcus onto transparent paper for each MRI slice ( fig. 2 A). From median to lateral slices, these traces first revealed the anterior peri-insular sulcus (the most medial peri-insular sulcus), lying 25–30 mm from the midline ( fig. 1 B). The superior peri-insular sulcus, the anterior insular sulcus, and the precentral insular sulcus were most often found on slices 30–35 mm from the midline ( fig. 1 C). Finally, the central insular sulcus (CIS), the posterior peri-insular sulcus, the postcentral insular sulcus, and the inferior peri-insu-lar sulcus (the most lateral peri-insular sulcus) were identified, respectively, on the slices 35–40 mm from the midline ( fig. 1 D).

Measurements Forty-four measurements were performed for each individual

insula. The major factors considered were: (1) the distance be-tween the AC and PC; (2) the length of insular and peri-insular sulci; (3) the angle between the CIS and the AC-PC line, and (4) the coordinates (y, z) of the 4 angle vertexes formed by the 4 sulci that limited the insula ( tables 1–3 ). Measurement inaccuracies re-lated mainly to slice thickness and pixel size, giving an estimated average error of 8 2 mm for stereotactic coordinates in the an-teroposterior and dorsoventral dimensions. An approximation of the surface of the insula was made by adding the surface areas of superior rectangular elements and inferior triangular elements fitted onto each insula ( fig. 2 B).

Digitalization Process and Statistical Analysis Preprocessing. The individual sagittal drawings of the insula

were scanned (200 pixels per inch resolution) and transferred to an image editing software (Photostudio Software). A manual re-finement was then performed to eliminate noise and attribute a 100% black color intensity to all lines of the drawings (resolution: 4 pixels, i.e., 0.6 mm) ( fig. 3 A).

Main Process. Drawings of the 75 individual insulae studied were superimposed using the PC center and AC-PC line as refer-ences. PC was chosen as the origin of reference (y = 0; z = 0 coor-dinates). Each drawing was weighted up to 1% of the grayscale intensity in order to obtain, for each subject, an image weighted with respect to the total number of drawings. Thus the color in-tensity of the resulting lines represented the likelihood of the cor-responding insular structure being at that same location. A 100% location probability for a given insular element corresponded to 75% pure black color. Finally, the Matlab software (Mathworks Inc.) was used to convert the different grayscale intensities into a colored scale, corresponding with the probability (ranging from 0% for blue to 100% for red) of finding a given insular element at a defined place ( fig. 3 B).

Statistical Analysis. p values ! 0.05 were considered as signifi-cant.

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VPC VAC

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Fig. 1. Reconstructing the insula from parasagittal MRI slices. T 1 -MRI slices, 4 mm thick. A Sagittal slice at the midline showing the AC = anterior commissure, PC = posterior commissure, AC-PC line = line passing through the superior edge of the AC and the inferior edge of the PC, VAC = lines orthogonal to the AC-PC line and tangential to the posterior edge of the AC, VPC = vertical lines orthogonal to the AC-PC line and tangential to the anterior edge of the PC. B 25 mm lateral to the mid-line. a = Anterior peri-insular sulcus. C 30 mm lateral to the midline. b = Superior peri-insular sulcus, c = anterior insular sulcus, d = precentral insular sulcus, e = posterior peri-insular sulcus. D 35 mm lat-eral to the midline. f = CIS, g = postcentral insular sulcus, h = inferior peri-insular sulcus.

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Fig. 2. A Individual drawing of the right insula in the AC-PC ref-erence system. SPS = Superior peri-insular sulcus; APS = anterior peri-insular sulcus; IPS = inferior peri-insular sulcus; PPS = pos-terior peri-insular sulcus; CCS = central cerebral sulcus; P1 = an-terior insular pole; P2 = posterior insular pole; L = insular limen. B Schematic insula. We calculated the indexed surface of the in-sula by separating it into two parts: a superior (rectangle) and an inferior (triangle) part. A = The distance between the superior extremity of CIS and the anterior angle of the insula; B = the dis-

tance between the superior extremity of CIS and the posterior angle of the insula; a = anterior angle of the insula; b = posterosu-perior angle of the insula; c = posteroinferior angle of the insula; d = inferior angle of the insula; I = anterior short gyrus; II = mid-dle short gyrus; III = precentral insular gyrus; IV = postcentral insular gyrus; V = posterior long gyrus; 1 = anterior insular sul-cus; 2 = precentral insular sulcus; 3 = CIS; 4 = postcentral insular sulcus; P1 = anterior insular pole; P2 = posterior insular pole; L = insular limen.

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Table 1. Mean length (in mm) of central insular and peri-insular sulci

APS SPS PPS IPS Below AC-PC

AboveAC-PC

Pole/VPC

CIS AC-PC CIS/AC-PC

Mean length, mm 26.23 49.29 13.78 30.8 16.16 19.23 33.77 29.48 23.96 62.68°95% CI

Lower limit 25.56 48.32 13.41 30.26 15.66 18.66 33.21 28.82 23.6 61.47°Upper limit 26.91 50.27 14.15 31.34 16.66 19.79 34.34 30.13 24.33 63.89°

Table 2. Vertex coordinates (y, z) of the 4 angles of the insula in the AC-PC reference system (PC: y = 0, z = 0)

AC-PC Anterior angle Posterosuperior angle Posteroinferior angle Inferior angle

y coordinates: y % y % y % y %

Mean length, mm 23.96 48.86 204.39 0.84 3.45 2.17 8.96 33.77 141.1895% CI

Lower limit 23.60 48.07 200.87 0.16 0.65 1.62 6.70 33.20 138.96Upper limit 24.33 49.64 207.92 1.51 6.26 2.72 11.2 34.33 143.41

z coordinates: z % z % z % z %

Mean length, mm 4.41 18.34 19.22 80.56 3.23 13.63 –16.16 67.6995% CI

Lower limit 3.71 15.45 18.66 77.93 2.75 11.60 –15.66 65.39Upper limit 5.11 21.23 19.78 83.19 3.71 15.67 –16.65 69.98

% = y and z coordinates (mm) as a percentage of AC-PC length; y defines the anteroposterior position (y = 0 at the intersection of the VPC with the AC-PC line); z defines the inferosuperior position (z = 0 on the AC-PC line).

Table 3. Distances (mm) between the anterior angle vertex of the insula and the superior extremity of the anterior, precentral and central insular sulci, expressed as a percentage of the superior (SPS) peri-insular sulcus length, and distance (mm) between the pos-terosuperior angle vertex and postcentral insular sulcus, expressed as a percentage of the posterior (PPS) peri-insular sulcus length

PPS SPS A I II III

mm % mm % mm % mm %

Mean length, mm 13.78 49.29 34.95 70.92 10.12 20.50 21.59 43.85 9.72 70.9295% CI

Lower limit 13.41 48.31 34.10 69.86 9.43 19.19 20.76 42.32 9.40 68.78Upper limit 14.14 50.26 35.80 71.97 10.80 21.81 22.42 45.37 10.03 73.06

APS = Anterior peri-insular sulcus; SPS = superior peri-insu-lar sulcus; PPS = posterior peri-insular sulcus; IPS = inferior peri-insular sulcus; below AC-PC = distance between the most infe-rior point of the anterior insular pole and the AC-PC; above AC-PC = distance between the most superior point of the superior

peri-insular sulcus and the AC-PC; pole/VPC = distance between the anterior insular pole and the VPC; CIS = central insular sul-cus; AC-PC = distance between the anterior and posterior com-missures; CIS/AC-PC = angle between the CIS and the AC-PC in degrees.

A = Distance between the anterior angle vertex of the insula and the superior extremity of the CIS in millimeters and as a per-centage of SPS length; I = distance between the anterior angle vertex and the superior extremity of the anterior insular sulcus in millimeters and as a percentage of SPS length; II = distance be-

tween the anterior angle vertex and the superior extremity of the precentral insular sulcus in millimeters and as a percentage of SPS length; III = distance between the posterosuperior angle vertex and the superior extremity of the postcentral insular sulcus in millimeters and as a percentage of PPS length.

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Results

Peri-Insular Sulci In every case, the insula was delimited by four peri-

insular sulci (anterior, superior, posterior, and inferior) ( fig. 2 ). The junction between the anterior and superior peri-insular sulci defined the anterior insular angle, the junction between the superior and posterior peri-insular sulci the posterosuperior insular angle, the junction be-tween the inferior and posterior peri-insular sulci the posteroinferior insular angle and the anterior insular pole specified the inferior insular angle ( fig. 2 B). Further data concerning the mean length of the peri-insular sulci, the distance between the anterior insular pole and the VPC and the statistical tests performed to reveal poten-tial sex and hemispheric differences are included in the tables.

Insular Sulci and Gyri The CIS subdivides the insula into two parts (anterior

and posterior). In 72 of the 75 hemispheres studied (96%), we found 5 distinct insular gyri. The anterior part of the insula was composed of 3 short gyri (anterior, middle, and precentral) separated by two short sulci (anterior and pre-central). These two short sulci stopped above the anterior insular pole. The posterior part of the insula contained two long and narrow gyri, the postcentral and posterior ones, separated by the postcentral insular sulcus. In the 3 remaining hemispheres (4%), we found 6 insular gyri, 4 of which were located in the anterior part of the insula.

We observed two insular poles in every case: (i) The anterior insular pole was the more inferior insular region, located below the lower part of the anterior short gyrus and sulcus. (ii) The posterior insular pole lays in the more anteroinferior portion of the posterior insula below the two long postcentral and posterior gyri and dorsal to the anterior insular pole. The insular limen separated these two poles ( fig. 2 A).

Topometry of the CIS The CIS divided the insula into two parts, anterior and

posterior. CIS length ranged from 23 to 39 mm (mean 29.48 mm; 95% CI: 28.82–30.1 mm ( table 1 ). We observed a positive linear correlation between the CIS and AC-PC lengths (Spearman test; r = 0.3014; p = 0.0086). The angle formed by the CIS with the AC-PC line ranged from 55 to 73° (mean 62.68°; 95% CI: 61.47–63.88°). In 74 out of the 75 hemispheres (98.6%), the CIS was uninterrupted. In 1 case (1.4%), this sulcus was interrupted in two dis-tinct parts. The CIS crossed the insula obliquely from the

limen to the superior peri-insular sulcus. Its superior ex-tremity was 9–23 mm (mean 14 mm; 95% CI: 13.91–15.13 mm) from the posterosuperior insular angle, 22–42 mm (mean 33.54 mm; 95% CI: 32.67–34.40 mm) from the an-terior insular angle and 8.5–23 mm (mean 15.32 mm; 95% CI: 14.66–15.98 mm) from the VPC. See tables 1–3 for further statistical analysis regarding the sex and side differences in CIS length.

Variability of the Insular and Peri-Insular Sulci The inferior peri-insular, central and postcentral in-

sular sulci were the least variable among all the insular and peri-insular sulci, with a localization probability of 35%. The anterior insular sulcus had the most variable location ( fig. 3 B).

Stereotactic Coordinates of the Insula We observed the posterior peri-insular sulcus at the

level of or just anterior to the VPC in 61 cases (81.3%). In the remaining 14 cases (18.7%), it was 0.5–7 mm poste-rior to the VPC. The projection of the posteroinferior an-gle of the insula was anterior to the PC in 74 out of 75 cases (98.6%). In the AC-PC reference system, the most inferior extent of the insula was its anterior pole and its most superior limit was the posterosuperior angle.

We found significant correlations between the y coor-dinate of the vertexes of the anterior (Spearman r = 0.36; two-tailed p = 0.001) and inferior (Spearman r = 0.5; two-tailed p = 0.0001) angles of the insula and the AC-PC length. We did not observe a similar correlation for the y coordinate of the posterosuperior and posteroinferior angle vertexes.

The above data allowed us to define, in the AC-PC ref-erence system, the coordinates for the insula with 100% certainty ( fig. 4 C) based on: (i) the vertex coordinates (y, z) for the angles of the insula, with respect to the AC-PC length ( table 2 ; fig. 4 A). (ii) the position of the superior extremity of the insular sulci (CIS, precentral, postcen-tral and anterior) in relation to the superior and posterior peri-insular sulci lengths ( table 3 ; fig. 4 B). (iii) The angu-lation between the sulci and the AC-PC line.

Surface of the Insula The surface index of the insula ranged from 726 to

1,363 mm 2 (mean 988.55 mm 2 ; 95% CI: 956.18–1,020.9 mm 2 ) when the 75 cases were considered all together. Al-though part of the data was not paired in all subjects studied, analysis of variance (two-way ANOVA; sex, side) showed effects of sex [F(3, 71) = 13.1; p = 0.0005] and side [F(3, 71) = 5.7; p = 0.02] on the insular surface index, with-

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out any interaction between sex and side. A similar test (repeated two-way ANOVA; sex, side) on the more lim-ited sample of paired values confirmed only the sex effect [F(3, 20) = 9.3; p = 0.01], with a mean index of 1,106 8 118 mm 2 for males and 944.4 8 91 mm 2 for females. Thus, our results did not verify the accepted interhemi-spheric asymmetry, favoring the left side [3] . However, our data agree with the pioneering observation made by Cunningham [4] , i.e., ‘In the adult brain the insula is pro-portionately longer in the male than the female.’

Method for Reconstructing the Insula A proportional representation of the insular cortex re-

quires only the positions of the AC, PC and the intercom-missural (AC-PC) length. (i) Using these data, the y and z coordinates of the four angle vertexes can be calculated using the proportional relationships which link these co-ordinates to the AC-PC length ( table 2 ; fig. 4 A). It is then possible to draw the four peri-insular sulci between the angle vertexes. (ii) The insular (anterior, precentral and central) sulci can easily be reconstructed by considering the length of the superior peri-insular sulcus and the dis-tances between the superior extremities of these insular sulci and the anterior insular angle vertex ( fig. 4 B). The mean angles of these insular sulci with AC-PC line are 108.5, 81.5 and 62.68°, respectively. We used a similar ap-proach for the postcentral insular sulcus, considering in this case the posterior peri-insular sulcus length and the distance between the superior extremity of the postcen-tral sulcus and the postero-superior insular angle vertex. The axis of this postcentral insular sulcus has a mean angle of 45.64° with the AC-PC line ( table 2 ; fig. 4 B). This strategy defines an area that contains the insula with a 100% probability ( fig. 4 C).

Discussion

Many anatomical studies [6, 8–10] have described the gross anatomy of the insula. Others have normalized the cerebral structures in the AC-PC reference or callosal baseline system [11, 12, 44–48] . More recently, three-di-mensional shape analysis of cortical folding patterns has normalized different cortical regions [13–22, 49–51] . In spite of these numerous studies, the insular cortex re-mains a blank spot in the cartography of the brain. To our knowledge, no studies have normalized the insular cor-tex with respect to its anatomical gyral and sulcal subdi-visions. These are the main findings of our study:

(1) The insula has a more complex shape than previ-ously supposed, being defined by 4 peri-insular sulci (an-terior, superior, posterior and inferior) instead of the 3 (anterior, superior, and inferior) classically described in the literature [6, 8, 10, 11, 52] . Our study allowed us to differentiate between the posterior peri-insular sulcus and the inferior peri-insular sulcus. These two sulci have two different axes separated by a clear angle (mean angle 126°). Interestingly, an embryology study shows the infe-rior sulcus becoming visible earlier than the posterior one, appearing at the 13th week as compared to the 17th week of gestation [53] .

(2) The CIS is a major landmark in this statistical rep-resentation of the insula.

(3) The morphology of the posterior insular sulcus varies less than its anterior counterpart. This may be due to the following reasons: (i) in the fetus, the inferior and posterior peri-insular sulci and the CIS develop first [53] , which gives them greater developmental and positional stability. (ii) Fetal development of the human brain shows that the temporoparietal operculum progresses around

Fig. 3. A Superimposing 75 individual insular drawings and their sulci using Photostudio software in the AC-PC reference system. a Superimposition of 75 insular outlines and their sulci. b Super-imposition of the postcentral insular sulcus and the precentral insular sulcus. c Superimposition of the 75 insular outlines to-gether with the CIS and the anterior insular sulcus. d Superimpo-sition of the insular surfaces. B Location probability using Matlab software. a Location probability of the 75 insular outlines and sulci (1 = central, 2 = precentral, 3 = postcentral, 4 = anterior). b Location probability of pre- and postcentral insular sulci. c Lo-cation probability of 75 insular outlines with the central and an-terior insular sulci. d The area in full red shows the insular region with 100% certainty. Fig. 4. Two-dimensional reconstruction of the insula based on statistical data. A Location of the 4 insular angle vertexes (a, b, c and d), using their y and z coordinates expressed as a function of

AC-PC length. The peri-insular sulci extend between the 4 angle vertexes. 1 = CIS; 2 = precentral insular sulcus; 3 = postcentral insular sulcus; 4 = anterior insular sulcus. B Proportional dimen-sions of the insular components. Distances between the anterior angle of the insula and the superior extremity of the anterior, pre-central and central insular sulci, as a percentage of the superior peri-insular sulcus length. Distance between the superior extrem-ity of the postcentral insular sulcus and the postero-superior an-gle of the insula, expressed as a percentage of the posterior peri-insular sulcus length. Note: in A and B , the mean position (full line) of each peri-insular sulcus with 8 confidence intervals (dot-ted lines). C The location of the insula – 100% probability. The points forming the angle vertexes of the trapezoid insula define this area (a, b, c and d), with coordinates of: a (y = 46; z = 4);b (y = 4; z = 16); c (y = 4; z = 4); d (y = 32; z = –16).

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*p < 0.05

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Fig. 5. Mean lengths of central insular and peri-insular sulci and statistical analysis. Although not all data were paired, we per-formed a two-way ANOVA (sex, side) on the length of each peri-insular sulcus to detect potential differences related to sex or hemispheric side. When we analyzed all 75 cases together, this analysis showed only a sex effect [F(3, 71) = 4.5; p = 0.03]. Males have significantly longer anterior peri-insular (p = 0.01) sulci on the right than females. A similar test (repeated two-way ANOVA;

sex, side) performed on the more limited, but paired, values for 12 patients confirmed this sex effect [F(3, 20) = 28.7; p = 0.0003] both on the left (male: 28.4 mm; female: 25.3 mm; p = 0.05) and the right (male: 27.9 mm; female: 23.8 mm; p = 0.01). A similar analy-sis of CIS length showed only a sex effect [F(3, 71) = 4.5; p = 0.03], with a longer CIS (male: 30.3 mm; female: 27.9 mm; p = 0.05) in males on the right side. However, testing paired values did not confirm this result.

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the posterior insula earlier than around the anterior in-sula. This closes the posterior aspect of the sylvian fissure before its anterior part. So, this opercularization process stops the extension of the posterior insular subdivision and the displacement of its sulci at the first stages of the fetal development [53] .

(4) The two-dimensional template of the insula is sim-ple and reproducible. With only the AC and PC positions and the intercommissural length, it is possible to perform a proportional reconstruction of the corresponding insu-lar cortex.

This method applies to the following cases: Neurosurgical Planning. For stereo-electroencephalo-

graphic exploration for epilepsy in particular, this meth-od could aid in reaching and then confirming the insular location of electrode contacts.

Localization of Insular Functional Areas. Anatomo-functional studies of the insula (using electrophysiologi-cal techniques, PET, fMRI) suggest it plays an important role in different functions [27, 29, 39, 41, 54, 55] . Until now, localization of these functions was only performed

by considering an anteroposterior subdivision. This igno-red the gyral and sulcal architecture and failed to sepa-rate the opercular region from the insula itself [56, 57] . Given the diversity of insular functions, it would be inte-resting to consider their location with respect to the gyral and sulcal anatomy. Our proposed proportional recon-struction of the insula could help with such an ap-proach.

Conclusion

Our study provides a precise morphological descrip-tion of the insular cortex and its variations. These data allow a blind proportional reconstruction of the insular cortex, with its sulcal and gyral architecture referenced to the AC-PC. This two-dimensional template of the in-sular lobe could help interpret anatomofunctional imag-ing studies and aid planning in insular stereotactic sur-gery.

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