Accepted Manuscript Analysis of the medial opticocarotid recess in patients with pituitary
macroadenoma using three-dimensional images Ryogo Kikuchi, MD, Masahiro Toda, MD, PhD, Sota
Wakahara, Hirokazu Fujiwara, MD, PhD, Masahiro Jinzaki, MD, PhD, Kazunari Yoshida, MD, PhD PII:
S1878-8750(16)30368-0 DOI: 10.1016/j.wneu.2016.05.094 Reference: WNEU 4155 To appear in:
World Neurosurgery Received Date: 6 March 2016 Revised Date: 28 May 2016 Accepted Date: 30
May 2016 Please cite this article as: Kikuchi R, Toda M, Wakahara S, Fujiwara H, Jinzaki M, Yoshida K,
Analysis of the medial opticocarotid recess in patients with pituitary macroadenoma using threedimensional images, World Neurosurgery (2016), doi: 10.1016/j.wneu.2016.05.094. This is a PDF file
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Kikuchi et al. 1 Title: Analysis of the medial opticocarotid recess in patients with pituitary
macroadenoma using three-dimensional images Authors: Ryogo Kikuchi MD1 , Masahiro Toda MD,
PhD1 , Sota Wakahara2 , Hirokazu Fujiwara MD, PhD3 , Masahiro Jinzaki MD, PhD3 , Kazunari Yoshida
MD, PhD1 . Affiliations: 1. Department of Neurosurgery, Keio University School of Medicine,
Shinjuku, Tokyo, Japan 2. Keio University School of Medicine, Shinjuku, Tokyo, Japan 3. Department
of Diagnostic Radiology, Keio University School of Medicine, Shinjuku, Tokyo, Japan MANUSCRIPT
ACCEPTED ACCEPTED MANUSCRIPT Kikuchi et al. 2 Corresponding Author’s name and complete
mailing address: Ryogo Kikuchi Department of Neurosurgery, Keio University School of Medicine 35
Shinano-machi, Shinjnku-ku, Tokyo 160-8582, Japan Phone: +81-3-3353-1211 Fax: +81-3-3354-8053
Email: fi020084@yahoo.co.jp Key Words: Opticocarotid recess; Pituitary adenoma; Threedimensional image. Running Title: Analysis of the medial opticocarotid recess in patients with
pituitary macroadenoma. MANUSCRIPT ACCEPTED ACCEPTED MANUSCRIPT Kikuchi et al. 3 Abstract
Object: The medial opticocarotid recess (MOCR), which contains the lateral tubercular recess (LTR), is
an important landmark for the cavernous internal carotid artery (ICA) and for accessing the parasellar
and suprasellar regions. These microanatomical landmarks for endoscopic endonasal surgery can be
observed using surgical simulation with three-dimensional images. The aim of this study was to
analyze the MOCR in patients with pituitary macroadenoma using three-dimensional images.
Methods: We constructed three-dimensional computed-tomography images in 20 patients with
pituitary macroadenoma and 20 patients with unruptured aneurysms as a control. Using these
images, we measured the distance between the left and right LTR, the midline and the unilateral LTR,
and the left and right ICA. Results: The distance between the left and right LTR was statistically longer
in the pituitary adenoma group versus the control group. Tumor volume were multivariate
parameters for the distance between the left and right LTR, which was significantly longer in the
group with tumor volumes > 5 cm3 versus the other groups. This distance was also significantly
correlated with the distance between the left and right ICA. MANUSCRIPT ACCEPTED ACCEPTED
MANUSCRIPT Kikuchi et al. 4 Conclusions: Pituitary macroadenomas expand the distance between
the left and right MOCR together with the distance between the left and right ICA. Introduction With
recent developments in the endoscopic endonasal approach (EEA), the medial opticocarotid recess
(MOCR) has become an important landmark for accessing the parasellar and suprasellar regions1,7.
Although it has been suggested that the MOCR is associated with the middle clinoid process1,7,10,
they are distinct structures8 . The MOCR is a teardrop-shaped osseous indentation formed at the
medial junction of the paraclinoid carotid canal and the optic canal, and is a key landmark for safe
expanded endoscopic approaches to the sellar and parasellar regions. The MOCR contains the lateral
tubercular recess (LTR), which is an osseous depression at the lateral edge of the tuberculum sellae8 .
These findings were obtained from cadaver studies. Three-dimensional (3D) modeling using
computed tomography (CT) provides direct visual information to identify and analyze the surgical
anatomy for EEA4 . Three-dimensional computed tomography (3D-CT) give the surgeon a clear
orientation because 3D-CT images versus MANUSCRIPT ACCEPTED ACCEPTED MANUSCRIPT Kikuchi
et al. 5 two-dimensional computed tomography images (2D) are very useful for demonstrating
carotid prominences, optic canals, and other bone structures in EEA4,6,11. 3D-CT images also show
the lateral opticocarotid recess (LOCR)6 , and therefore the MOCR is more easily detected in 3D-CT
images. Enlargement of the sellae turcica is a classical finding by conventional X-ray studies in
pituitary macroadenoma. Pituitary macroadenoma patients were more likely to have prominent
sellae and widened sellar face than were healthy adults in the study using magnetic resonance
imaging (MRI)13. These results indicate that the slow growth of the tumor results in bone
remodeling. However, there are no reports on how the external skull base structure like the MOCR or
the LOCR changes by pituitary macroadenoma. The aim of the present study was therefore to reveal
whether pituitary macroadenoma affects the external skull base structure and especially the MOCR
using 3D-CT images. MANUSCRIPT ACCEPTED ACCEPTED MANUSCRIPT Kikuchi et al. 6 Materials and
Methods Patients We declare that all human and animal studies were approved by the Ethics
Committee of Keio University School of Medicine and have therefore been performed in accordance
with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
We declare that all patients gave informed consent prior to inclusion in this study. Preoperative
enhanced CT was performed on 20 patients who underwent EEA for pituitary macroadenoma
without GH-secreting adenoma. Patients were enrolled from April 2013 to June 2015 . As a control,
preoperative enhanced CT was also performed on 20 patients who underwent clipping or coiling for
an intracranial unruptured aneurysm that was not located in the internal carotid artery (ICA) region.
3D-CT image reconstruction All preoperative contrast-enhanced CT examinations were performed
with a 320-detector row CT scanner (Aquilion One; Toshiba Medical Systems, Otawara, Japan)5 . All
CT data were processed using the AW server (GE Healthcare, Japan) in an electric chart terminal.
MANUSCRIPT ACCEPTED ACCEPTED MANUSCRIPT Kikuchi et al. 7 We used 2 CT series for each
patient’s 3D image reconstruction, mask volume data, and arterial phase imaging. 3D bone images
were constructed using volume rendering and front-cut methods. Then, 3D arterial images were
constructed using volume rendering and no-cut methods. Two images were merged and an obliquecoronal selection was made through the nose to the tumor. Analysis parasellar microanatomy in 3DCT images Midline was pointed on the line between the internal occipital protuberance and the crista
galli in axial plane and was indicated in 3D-CT images. Using 3D-CT images, we evaluated the optic
canal, the carotid prominence, the MOCR, the LTR, and the LOCR. The LTR was defined as the
depressed point at the confluence of the optic canal, the carotid canal, the upper portion of the
sellae, and the anterior cranial base. The distance between the left and right LTR (LTR-LTR) was
measured. Furthermore, we measured the distance between the midline and the unilateral LTR (MidLTR) on both sides (Fig. 1). The maximum distance between the right and left carotid arteries in the
cavernous portion (ICA-ICA) was measured. In patients with pituitary adenoma, we assessed the
maximum MANUSCRIPT ACCEPTED ACCEPTED MANUSCRIPT Kikuchi et al. 8 tumor diameter, tumor
volume, and Knosp’s grade using preoperative contrast enhanced MRI. All images were analyzed
three times by two neurosurgeons and one medical student. Statistical analysis was performed using
SPSS statistical software (IBM). Comparisons of measurements between the pituitary adenoma group
and the control group were performed using the Student’s t test or the Mann-Whitney
nonparametric test. Univariate and multivariate analyses were performed with the linear and the
multiple regression model to determine associations between LTR-LTR and characteristics in patients
with pituitary adenoma. A one-way analysis of variance (ANOVA) was used to compare the LTR-LTR
of the control group with those of the groups with tumor volumes less than and more than 5 cm3 .
The Pearson correlation coefficient between LTR-LTR and ICA-ICA was computed. P values < 0.05
were considered statistically significant. Results MANUSCRIPT ACCEPTED ACCEPTED MANUSCRIPT
Kikuchi et al. 9 Patient characteristics and measurements are shown in Table 1. LTR-LTR and Mid-LTR
were statistically wider in the pituitary adenoma group versus the control group. The MOCR was
detected on 37 sides (92.5%) in the control group and on 39 sides (97.5%) in the pituitary adenoma
group. The LOCR was detected on 21 sides (52.5%) in the control group and on 21 sides (52.5%) in
the pituitary adenoma group. Attachment of sphenoid septum disturbed detection of the MOCR and
the LOCR. Associations between LTR-LTR and characteristics in pituitary adenoma patients are shown
as Table2. Tumor volume were multivariate parameters for LTR-LTR. The LTR-LTR in male patients
(average 16.9 mm; range 12.7-20.7 mm) tended to be greater than that in female patients (average
14.6 mm; range 10.2-18.8 mm) (p=0.075). LTR-LTR was significantly greater in the group with tumor
volumes more than 5 cm3 versus the group with tumor volumes less than 5 cm3 and the control
group (Fig. 2). In the pituitary adenoma group, the correlation coefficient between LTR-LTR and ICAICA was significant (Pearson correlation r=0.740, p=0.000). MANUSCRIPT ACCEPTED ACCEPTED
MANUSCRIPT Kikuchi et al. 10 Discussion Enlargement of the sellae turcica is a classical finding by
conventional X-ray studies in pituitary macroadenoma. Widening of distance between the
intercavernous parasellar ICAs and width of the sellar face were found in the patients with sellar
lesions. These findings suggest that slow vertical tumor growth results in bone remodeling and ICA
deviation9,13. Otherwise, there are no reports about pituitary adenoma affecting parasellar bone
structure except for sellar ballooning. In this study, we focused on how the MOCR and the LTR are
affected by pituitary macroadenoma using 3D images. LTR-LTR and Mid-LTR were wider in the
pituitary adenoma group versus the control group. Pituitary tumor volume significantly affected LTRLTR. LTR-LTR increased significantly in the group with tumor volumes more than 5 cm3 . These results
indicate that pituitary macroadenoma tends to produce a wide entrance for EEA. In addition, skull
size could affect LTR-LTR, because sex tended to affect LTR-LTR and skull size tends to be wider in
males than in females. The MOCR and the LOCR have been related to the ICA in previous
reports2,8,10 . Displacement of the intracavernous ICA was found in patients with sellar regions and
MANUSCRIPT ACCEPTED ACCEPTED MANUSCRIPT Kikuchi et al. 11 was associated with cavernous
sinus invasion in patients with pituitary adenoma3,12,13. In this study, ICA-ICA correlated with LTRLTR significantly in pituitary adenoma patients. We verify that the LTR and the MOCR are consistently
useful landmarks for the cavernous ICA with or without disease. Furthermore, these results suggest
that slow-growing pituitary macroadenoma expands the cavernous ICA and parasellar bone
structures together as previously described13 . The present study was conducted using 3D-CT images
for simulated operation in EEA6 . Detailed bone structures like recesses and prominences are better
understood using 3D images versus 2D images. By analyzing 3D-CT images and making comparisons
with a control group, we documented external skull base changes in patients with pituitary adenoma.
Surgical simulation using 3D images may therefore provide important information. While cadaver
studies have been used as a general investigation method and have provided various information for
microsurgical anatomy, future anatomical analyses based on 3D images should be considered for
demonstrating individual slight anatomical differences. MANUSCRIPT ACCEPTED ACCEPTED
MANUSCRIPT Kikuchi et al. 12 Conclusions Pituitary macroadenomas expand the distance between
the left and right MOCR together with the distance between the left and right ICA, especially in cases
where the tumor volume is more than 5 cm3 . 3D-CT images may efficiently provide information
about bone structures for EEA. Disclosure The authors report no conflict of interest concerning the
materials or methods used in this study or the findings specified in this paper. Acknowledgments:
The authors would like to thank Takayuki Abe , PhD, Assistant Professor, Department of Preventive
Medicine and Public Health, Keio University School of Medicine, for the statistical analysis of our
measured results. References 1. Cavallo LM, De Divitiis O, Aydin S, Messina A, Esposito F, Iaconetta G,
et al.: MANUSCRIPT ACCEPTED ACCEPTED MANUSCRIPT Kikuchi et al. 13 Extended endoscopic
endonasal transsphenoidal approach to the suprasellar area: Anatomic considerations - Part 1.
Neurosurgery 62:24–34, 2008 2. Chicco P, Magnussen JS, Vu DH, Van Wall H Der: Expanding the
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8. Labib MA, Prevedello DM, Fernandez-Miranda JC, Sivakanthan S, Benet A, Morera V, et al.: The
medial opticocarotid recess: an anatomic study of an endoscopic “key landmark” for the ventral
cranial base. Neurosurgery 72:66–76, 2013 9. Ouaknine GE, Hardy J: Microsurgical anatomy of the
pituitary gland and the sellar region. 2. The bony structures. Am Surg 53:291–7, 1987 10. Peris-Celda
M, Kucukyuruk B, Monroy-Sosa A, Funaki T, Valentine R, Rhoton AL: The recesses of the sellar wall of
the sphenoid sinus and their intracranial relationships. Neurosurgery 73:117–131, 2013 11. Raappana
A, Koivukangas J, Pirila T: 3D modeling-based surgical planning in transsphenoidal pituitary surgery-preliminary results. Acta Otolaryngol 128:1011–1018, 2008 12. Vieira JO, Cukiert A, Liberman B:
Evaluation of magnetic resonance imaging MANUSCRIPT ACCEPTED ACCEPTED MANUSCRIPT Kikuchi
et al. 14 criteria for cavernous sinus invasion in patients with pituitary adenomas: Logistic regression
analysis and correlation with surgical findings. Surg Neurol 65:130– 135, 2006 13. Zada G, Agarwalla
PK, Mukundan S, Dunn I, Golby AJ, Laws ER: The neurosurgical anatomy of the sphenoid sinus and
sellar floor in endoscopic transsphenoidal surgery. J Neurosurg 114:1319–1330, 2011 MANUSCRIPT
ACCEPTED ACCEPTED MANUSCRIPT Kikuchi et al. 15 Figure legends Figure 1: 3D images constructed
from preoperative computed tomography data in patients with pituitary adenoma (A, C and E) and
corresponding endoscopic views during surgery (B, D and F). A, B, a 3D image (A) and the
corresponding endoscpic view (B) shows sphenoid septum attached near the midline of the sellae.
The distance between the left and right lateral tubercular recess (LTR-LTR) is 15.9 mm (a), the
distance between the midline and the right lateral tubercular recess (right Mid-LTR) is 9.6 mm (b),
and the distance between the midline and the left lateral tubercular recess (left Mid-LTR) was 6.3
mm (c). C, D, a 3D image (C) and the corresponding endoscopic view (D). Sphenoid septum is not
attached sellae. LTR-LTR is 13.1mm (d), right Mid-LTR is 7.4mm (e) and left Mid-LTR is 5.7 mm (f). E,
F, right sphenoid septum attached the right optic canal, which disturbed detection of the right lateral
tubercular recess and the right lateral opticocarotid recess in a 3D image (E). In the corresponding
endoscopic view, similar findings are observed (F). Left Mid-LTR is 6.3mm (g). MANUSCRIPT
ACCEPTED ACCEPTED MANUSCRIPT Kikuchi et al. 16 The optic canal (*), the LTR (▲), the lateral
opticocarotid recess (■), and the medial opticocarotid recess (teardrop shaped blue line). Figure 2:
The relationship between tumor volume and the distance between the left and right lateral
tubercular recesses. Solid transverse black line is the median, edges of boxes are first and third
quartiles, and error bars are maximum and minimum values. LTR-LTR, the distance between the left
and right lateral tubercular recesses; NS, not significant. MANUSCRIPT ACCEPTED ACCEPTED
MANUSCRIPT Table 1. Patient characteristics and measurements Control (n=20) Pituitary tumor
(n=20) p value Sex Male 8, Female 12 Male 10, Female 10 0.537 Age (range) (y/o) 63.8 (55-77) 61.3
(31-79) 0.513 Maximum diameter of tumor (range) (mm) NE 30.75 (16.09-45.57) NE Tumor volume
(range) (cm3 ) NE 8.54 (1.12-19.04) NE Knosp grade (range) NE 2.7 (0-4) NE ICA-ICA (range) (mm)
13.4 (6.5-16.6) 16.4 (11.5-23.8) 0.005 LTR-LTR (range) (mm)*1 13.0 (8.0-19.7) 15.7 (10.2-20.7) 0.005
Mid-LTR (range) (mm)*2 6.4 (3.5-10.6) 7.8 (4.5-11.8) 0.007 *1: control (n=17), Pituitary Tumor
(n=19), *2: control (n=37), Pituitary Tumor (n=39). ICA-ICA, the maximum distance between the left
and right carotid arteries in the cavernous portion; LTR-LTR, the distance between the left and right
lateral tubercular recesses; Mid-LTR, the distance between the midline and the lateral tubercular
recess. MANUSCRIPT ACCEPTED ACCEPTED MANUSCRIPT Table 2. Univariate and Multivariate
analysis of the distance between the left and right lateral tubercular recesses in patients with
pituitary adenoma Variables Regression coefficient ± SE p value Univariate Analysis Age -0.070 ±
0.042 0.116 Sex -2.341 ± 1.235 0.075 Knosp grade 1.173 ± 1.345 0.668 Maximum tumor diameter
0.124 ± 0.075 0.116 Tumor volume 0.277 ± 0.114 0.027 Multivariate Analysis Sex -2.172 ± 1.081
0.062 Tumor volume 0.264 ± 0.105 0.023 SE, standard error. MANUSCRIPT ACCEPTED ACCEPTED
MANUSCRIPT MANUSCRIPT ACCEPTED ACCEPTED MANUSCRIPT MANUSCRIPT ACCEPTED ACCEPTED
MANUSCRIPT Highlights The MOCR is an important landmark for endoscopic endonasal surgery. The
LTR which is a part of MOCR can be observed using 3D images. LTR-LTR was longer in the pituitary
adenoma group versus the control group. LTR-LTR was longer in the group with tumor volumes > 5
cm3 versus the other groups. Pituitary macroadenomas expand the MOCR together with the ICA.
MANUSCRIPT ACCEPTED ACCEPTED MANUSCRIPT Abbreviations list: CT: computed tomography DSA:
digital subtraction angiography EEA: endoscopic endonasal approach ICA: internal carotid artery ICAICA: the maximum distance between the right and left carotid arteries in the cavernous portion
LOCR: lateral opticocarotid recess LTR: lateral tubercular recess LTR-LTR: the distance between the
left and right LTR Mid-LTR: the midline and the unilateral LTR MOCR: medial opticocarotid recess
MRI: magnetic resonance imaging 2D: two-dimensional computed tomography images 3D: threedimensional MANUSCRIPT ACCEPTED ACCEPTED MANUSCRIPT 3D-CT: three-dimensional computed
tomography MANUSCRIPT ACCEPTED ACCEPTED MANUSCRIPT The authors report no conflict of
interest concerning the materials or methods used in this study or the findings specified in this paper.