Experiences of Using Hybrid Operating Rooms in the Treatment of large or giant Carotid-Ophthalmic Aneurysms

Background: A hybrid operating room (Hybrid-OR) was a surgical theatre combined conventional operating room with advanced medical imaging devices. There were still plenty of limitations when endovascular treatment or microsurgical treatment was used individually to deal with large or giant carotid-ophthalmic aneurysms. The purpose of this study was to explore and summarize the technical features and effectiveness of the application of Hybrid-OR in dealing with major intracranial carotid-ophthalmic aneurysms. Methods: The department of neurosurgery treated 12 cases of large or giant intracranial carotid-ophthalmic aneurysms between March 2013 and December 2015 with Hybrid-OR. All cases were treated with clipping and parent vessel reconstruction. Results: With the assistance of Hybrid-OR, the rate of incompletion of intraoperative aneurysm clipping decreased from the original 25% ( 3/12) to 0%, while the rate of vessel stenosis decreased from the original 16.7% (2/12) to 8.35% (1/12). For thromboembolic event, there was one ischemic infarction complication occurred in only one patient, and none of patients appeared embolic infarction complication. All 12 patients were followed up for an average of 3 years and no aneurysms recurred. The postoperative recovery conditions were evaluated with the modified Rankin Scale (mRS): 11 patients showed no symptoms (mRS 0), 1 patient showed slight disability (mRS 1-2), and none of the cases showed severe disability (mRS 5) nor death (mRS 6). Conclusion: The Hybrid-OR provides new ideas to the surgical clipping the large or giant intracranial carotid-ophthalmic aneurysms, which effectively decreased the rate of intraoperative vessel stenosis and unsuccessful clippings.


Background
Intracranial carotid-ophthalmic aneurysm referred to the aneurysm that originates from the distal dural ring of the internal carotid artery (ICA) at the top of the cavernous sinus to the origin of the posterior communicating artery (PComA). It was known as a C6 aneurysm or para-clinoid aneurysm which accounted for about 5% of intracranial aneurysms. [1,2] The rates of fatality and disability were relatively high since its location of growth, complexity and specificity of ophthalmic segment aneurysm. [1,2] Although endovascular and micro-neurosurgical technologies have been developing rapidly, ophthalmic segment aneurysms, especially for the large (diameter = 10-25 mm) and giant (diameter > 25 mm) ones, were still considered as a challenge for surgeons.
Hybrid operating room (Hybrid-OR) was known as the "one-stop" operating room. In a broad sense, it indicated that one operating room was equipped with multiple medical examination devices and operation assisting devices. For instance, intraoperative MRI and navigation devices, and other treatment equipment was included so that imagological examinations, tracking, navigation assistance and multiple surgical approaches could be combined to perform in one operating room. In a narrow sense, Hybrid-OR indicated that endovascular-surgical combined operating rooms not only retain the advantages of traditional open operations (visibility and convenience for operating and navigating), but also kept the advantages of endovascular operations (less trauma and multiple endovascular assisting approaches).
Hybrid operation was originally defined by Angelina et al. [3] in 1996, and firstly used for the cardiac operation. Recently, the hybrid operation has been providing new ideas for neurosurgeons in treating cerebrovascular diseases. Our hospital completed the building of Hybrid-OR in 2011, which effectively treated 12 intracranial large and giant carotid-ophthalmic aneurysm cases between March 2012 and December 2015, and its effectiveness was summarized in our study.

Methods
Clinical data and Imageology data During the period from March 2013 -December 2015, our department of neurosurgery applied Hybrid-OR in a treating large and giant carotid-ophthalmic aneurysm in 12 cases: 5 male cases and 7 female cases. The ages of these patients ranged from 53 to 68 years old with a mean of 53.9 years.
All cases showed unruptured intracranial aneurysms, including 5 cases of chronic headache, 4 cases of visual impairment, and 3 cases of visual field defects.
All cases were diagnosed with computed tomography angiography (CTA), magnetic resonance imaging (MRI), preoperative digital subtraction angiography (DSA) and 3D-DSA examinations. And the ICA balloon occlusion test (BOT), cross circulation test and Allcock's test were performed to understand the condition of cerebral blood flow compensation.12 patients were diagnosed with 12 large or giant aneurysms. The maximum diameter of the aneurysmal dome varied from 10.5 to 38.1 mm, the neck measured from 3.9 to 15.4 mm and the dome-neck (D/N) ratio varied from 1.4 to 9.8. Summary of demographic and clinical characteristics of 12 patients are shown in Table 1. when the neck of aneurysm ≥ 8 mm, the balloon was deployed across the neck of the aneurysm; when the neck of aneurysm < 8 mm, the balloon was deployed in C2 -C3 of ICA. Based on this principle: the balloon was placed in the C2 -C3 segment of ICA for 7 cases (1, 4, 6, and 8-11) and across the aneurysm neck for 5 cases (2, 3, 5, 7 and 12), and the balloons kept deflated after initial deployment. Neither pre-procedural nor intra-procedural antiplatelet, systemic heparinization agents were administered.
Second, the head was secured by a carbon fiber fixation system, and the electrophysiological monitoring was used. Conventional pterional approach: using the intradural anterior clitoridectomy (IAC) technique to remove the anterior clinoid process (ACP). The distal dural ring (DDR) of the opticsheath was opened to sufficiently dissociate the nerve from the aneurysm neck.
Third, the balloon would be inflated to block the ICA when clipping the aneurysm. After the aneurysms clipped, intraoperative DSA was administered repeatedly to identify residues of the aneurysms neck and vessel stenosis because of incorrect clipping. If the clipping was not ideal, then the clip would be readjusted to achieve the best effect.

Results
Residual aneurysm necks were discovered by the intraoperative DSA in 3 cases (1, 2 and 7): for these 3 cases, the residual aneurysm necks were successfully clipped by adjusting the clips, that were verified by the second intraoperative DSA. With the assistance of Hybrid-OR, the rates of the residual aneurysm necks decreased from the original 25% (3/12) to 0%.
Vessel stenosis were found in 2 cases (1 and 2) by the intraoperative DSA: for case 1, clipping was readjusted, and second intraoperative DSA displayed that the stenosis of the parent carotid artery and ophthalmic artery was relieved; while for case 2, clipping was readjusted, but mild stenosis of the parent ICA still remained as severe atherosclerosis in the aneurysm neck. To clip the aneurysm and reconstruct the right ICA, she was offered both surgical and endovascular treatment, along with alternatives, risks, and benefits. The management plan was formulated to proceed with the hybrid operation as an elective procedure. In the operation, we put the balloon was placed in the C2 -C3 segment of ICA due to a relatively narrow-necked aneurysm (D/N ratio 5.6). Then we did craniotomy by taking pterional approach: using the IAC technique to remove the ACP. Then we found the right optic nerve was compressed by the giant aneurysm and the optic nerve is crossed by the aneurysm neck; removal of the anterior clinoid process and dissociation of the optic nerve from the aneurysm neck to sufficiently reveal the aneurysm neck (Fig. 1C&D). After the placement of the first clip, the first intraoperative DSA displayed that the aneurysm had been clipped and small amounts of the residue of the aneurysm neck (Fig. 1E&F). A supplementary miniature clip was placed during the operation. The second intraoperative DSA displayed that the aneurysm had been completely clipped. However, stenosis occurred in the ICA (white arrow) with poor visualization of the optic artery (black arrow) and poor visualization of the distal branch vessel of ICA ( Fig. 1G&H). A miniature clip with angular tips was used to replace the original one. The third intraoperative DSA displayed that the aneurysm was completely clipped. The ICA with stenosis had been relieved (white arrow) and the visualization of the optic artery and distal branch vessel of MCA was effectively improved (black arrow) (Fig. 1I&J).

CASE2: Female patient, 54 years old
A 54-years-old woman presented with a 6-month history of chronic headache. MRI and pre-operation DSA provided the diagnosis of a 21.4-mm large carotid-ophthalmic aneurysm with a 13.4-mm wide neck. (Fig. 2A&B) A combined approach was offered in the Hybrid-OR. Firstly, a 4 mm x 20 mm balloon (Hyperglide; Micro Therapeutics, Inc., Irvine, CA) was deployed across the ophthalmic aneurysm neck, and the balloon was inflated (Fig. 2C&D). The aneurysm softened sufficiently to place two arrays of straight fenestrated and angled fenestrated clips (Aesculap AG, Tuttlingen) on the aneurysm. After that, the second intraoperative DSA was performed and found the bulk of aneurysm was clipped and not visualized, but a small portion of the aneurysm was residue and visualized ( Fig. 2E&F). After adjusting clips, the third intraoperative DSA displayed the aneurysm was completely clipped, but the parent artery was slightly narrowed due to the severe calcification of the aneurysmal neck (Fig. 2G&H). Due to the size of the carotid-ophthalmic aneurysms, the aneurysm necks located in ICA leading to the skull, around the ACP, and the optic nerve blocked the field of vision. As a result, finding the aneurysm neck and its branches through craniotomy would be difficult due to blind spots. Especially large and complex intracranial aneurysms, the aneurysm neck might be obstructed which could lead to it rupturing before clipping. [5] As reported in the literature, after conventional aneurysm clipping with intraoperative indocyanine green (ICG) video angiography check, post-operation DSA showed the rate of incompletion of aneurysm clippings was at 6.3% while parent vessel stenosis was 5.7%. For giant aneurysms, the rates of incompletion of clippings and occurrence of stenosis were as high as 15% even more. [6] So, compared to intraoperative DSA, intraoperative ICG could not demonstrate clearly and accurately images of parent vessel stenosis and aneurysm neck residues due to blocked vision and other reasons. Besides, intraoperative ICG was not able to directly observe the situation of the distal blood vessels.

Limitations of Intra-Arterial Embolization for Treating Giant Carotid-Ophthalmic Aneurysms
Recently, interventional treatments for intracranial aneurysms have been in rapid development, which could reveal its advantages in treating intracranial aneurysms. Currently, usable interventional technologies in treating complex wide-necked aneurysms are balloon-assisted coiling embolization, stent-assisted embolization and dual micro-catheter coiling embolization. However, a wide-necked aneurysm with complex conformation was difficult to be totally removed by endovascular treatments.
Although new interventional devices, tools, and technologies are evolving, a variety of interventional techniques are techniques challenging for treating giant carotid-ophthalmic aneurysm. For the method of stent-assisted coiling embolization, it is possible that the stent guidewire could not overcome the technical difficulties of placing the stent through an aneurysm. The stent is used in stent-assisted coiling embolization to reconstruct the parent vessel and set as a block on the aneurysm neck and to prevent coil dislocation. However, within a few months of surgery, dual antiplatelet therapy (DAPT) must be strictly performed to the patients until the internal membrane of the parent vessel has completely regenerated before the aneurysm neck. [7] Therefore, in most cases, stent-assisted coiling embolization technology could not be safely used to treat ruptured aneurysms. [8] Carotid-ophthalmic aneurysms often show mild symptoms or none until they grow to a larger size due to their unique anatomic features. It was reported 30-50% of patients who have had carotidophthalmic aneurysms grown to giant size (diameter > 25 mm) on their first visit to the hospital. The main symptoms are often loss of vision and visual field defects. [9] And intervention embolization was used to treat these patients; however, the aftermath of the aneurysm could not be eliminated, and the symptoms were not only not alleviated after the operation, but also keep growing progressively which requires craniotomy to remove emboli in order to save the patient's' vision and visual field [10,11]. Moreover, carotid-ophthalmic aneurysms often contain important vessels or artery branches which originates from the aneurysm dome or fundus parts such as the ophthalmic artery, PComA, and even anterior choroidal artery (AChA).
Under these circumstances, the ideal treatments were to reconstruct the parent vessel based on retaining important perforator vessels and its branches. In this case, using the common interventional embolization technologies and flow-directed devices to solve the aforementioned problem was pretty difficult. Furthermore, another difficulty in treating giant complex carotid-ophthalmic aneurysms was the high risk of relapse after surgery. As reported, the incidences of relapse after carotid-ophthalmic aneurysm operations ranged 27.4 to 31.6%, [12][13][14] however, the rates of relapse after interventional embolization had reached 50% in treating giant aneurysm. [15] Therefore, It was extremely difficult to use the interventional embolization method to treat patients with wide-necked, giant and/or branch vessel accumulated carotid-ophthalmic aneurysms.
In recent years, the flow diverters (e.g. SILK embolization device, Pipeline embolization device) have and (IV) dealing with ACP using the IAC technique rather than EAC technique, and no need to totally remove ACP, but removed a part of ACP in accordance with operational needs. IAC technique was safer and more timesaving than EAC.
Secondly, compared to direct observe under the microscope or interoperation ICG technique, it's more clearly and accurately to evaluate the effect of aneurysm-clipping using the intraoperative DSA.

Conclusion
In summary, microsurgical clipping, intraoperative ICG, and intraoperative monitoring techniques continued improving and progressing, and clipping of complex intracranial aneurysms is becoming increasingly safer. In accordance, balloons, stents and flow diverters make the treatment more and more familiar. However, there are still plenty of limitations and technical bottlenecks when these two types of methods are used individually. As Hybrid-OR comes to light, it provides a safer and more promising treatment platform for neurosurgery, providing a completely new concept for the treatment of intracranial aneurysms. Currently, our neurosurgery department has gained initial experiences. In

Ethics approval and consent to participate
The studies involving human participants were reviewed and approved by Tianjin Medical University General Hospital ethics committee, the patients/participants provided their written informed consent to participate in this study.

Consent for publication
Written informed consents for the publication of personal data and images were obtained from all patients.    intraoperative DSA displayed that the bulk of aneurysm was clipped and not visualized, but a small portion of the aneurysm was residue and visualized. Figure2G&H: After adjusting clips, the third intraoperative DSA displayed the aneurysm was completely clipped, but the parent artery is slightly narrowed due to the severe calcification of the aneurysmal neck.