Mixed Reality Applied to Surgical Planning and Tailoring of Carotid Endarterectomies

Mixed Reality Applied to Surgical Planning and Tailoring of Carotid Endarterectomies | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Mixed Reality Applied to Surgical Planning and Tailoring of Carotid Endarterectomies Elisa Colombo, Marcella Cavelli, Luca Regli, Jorn Fierstra, Martina Sebök, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7722134/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Purpose Perioperative three-dimensional (3D) anatomical visualization with mixed reality (MxR) may have a relevant impact on adequate carotid endarterectomy (CEA) planning compared to standard imaging studies, by highlighting patient specific anatomical features and allowing the rehearsal of the relevant surgical steps in 3D. Methods All consecutive CEAs planned with MxR between January 2022 and July 2024 were prospectively included. Using the preoperative head and neck CT-angiography (CTA) and/or MR-angiography (MRA), skin, skull, cervical spine and vascular anatomy including plaques were segmented. The resulting 3D interactive hologram was matched on the patient with MxR glasses in the operating room after patient positioning and drawing initial skin incision. The impact of 3D visualization on surgical planning and anatomical understanding was documented and usability testing was performed. Results Forty-nine CEAs were included. Mean hologram’s preparation time was 17+/-8 minutes. Mean duration of intraoperative hologram’s use was 5 +/- 2 minutes. The supervising surgeon significantly altered (shortening) the skin incision in 16 cases (33%). Higher scores were given to the domains Ease of Use and Satisfaction. Conclusions CEA planning with MxR seems to have an impact on anatomical understanding for both less experienced neurosurgeons and highly experienced neurosurgeons performing more than 25 CEAs per year. Future research should focus on quantification of the benefits in surgical training and assess the impact on surgical outcomes. mixed reality carotid endarterectomy surgical revascularization cerebral ischemia 3D visualization surgical planning Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Carotid endarterectomy (CEA) represents the first line of treatment for high-grade symptomatic and asymptomatic carotid artery stenosis worldwide. 1 This surgical procedure has been introduced in the 1950s and has been developed and extensively studied worldwide. The optimal performance of CEA requires experience and training as well as a precise knowledge and understanding of the patient neck anatomy. 2 The carotid bifurcation lies normally at the level of the vertebral bodies of C3-C4. 3 However this is highly variable and cases of high or low bifurcation must be carefully examined to choose the best therapy (surgery or endovascular, in case of very high or very low carotid location of the plaque). 2 , 4 Also vessels’ tortuosity (i.e.: loop or kinking) or anomalies (i.e.: side-by-side carotid) and variations in its branching pattern can occur. Surgeons should take these variations into consideration for surgical planning. However, all these variations may not be adequately projected in three dimensions (3D) by viewing only two-dimensional (2D) imaging. 4 Mixed Reality (MxR) could be a suitable technology for better 3D visualization and anatomical understanding and could lead to better surgical planning as well as intraoperative visualization of the patient-specific anatomy. 5 MxR is a form of Augmented Reality (AR) featured by the overlay of a 3D stereoscopic interactive reconstruction of the patient anatomy, a so-called hologram, over the real world’s anatomy using a head mounted display (HMD), thus without losing the perception of the reality around the hologram. This connection substantially augments not only the anatomical appreciation, but also the spatial orientation and comprehension of the anatomical relationships among healthy and pathologic structures. 6 Therefore, MxR could optimize the surgical planning, increase intraoperative efficiency, decrease intraoperative adverse events and improve surgical outcomes. The authors present in this study the experience gathered on MxR application for carotid endarterectomies (CEAs), focusing on the impact on patient-specific anatomical understanding and surgical planning. Materials and Methods The local review board approved the present study before its performance. All included patients signed an informed consent to give permission to the surgical procedure and to the publication of their clinical and radiological data under general KEK PB_2017_00093/NCT01628406 (Kanton of Zurich Ethical Committee). The present study has been performed in accordance to the principle of the Declaration of Helsinki. Patient clinical and radiological data Consecutive patients who underwent CEA surgery planned with MxR between January 2022 and July 2024 at our institution were included in the analysis. Surgical indication to CEA was given on the basis of ICA stenosis percentage, calculated according to the NASCET criteria, vessel angioanatomy and clinical presentation. 7 All the surgical indications were discussed interdisciplinary either at the cerebrovascular board of our Institution (neurologists, neurosurgeons and neurointerventionalists) or case by case. Preoperative and postoperative modified Rankin scale (mRS) and National Institute of Health Stroke Score (NIHSS) were collected for every patient. Each CEA was performed according to the state of art microsurgical technique. 8 – 11 Using the preoperative imaging (head and neck CTA and/or MRA), data on plaque presence as well as its position and morphology, carotid bifurcation level (based on cervical vertebral bodies), anatomical variations (side-by-side carotid or abnormal ECA branch origin, i.e. anatomical variations of thyroid artery), carotid vessels’ tortuosity (kinking and loops) were recorded. Data on postoperative imaging control (CTA) performed within 48 hours from the procedure and postoperative adverse events during the hospital stay were also gathered. Segmentation process and hologram preparation Using the preoperative radiological studies as source imaging source in the form of Digital Images and Communication in Medicine (DICOM), the CCA, ECA and ICA, as well as the plaques presenting calcifications (when clearly evident) were semi-automatically and manually segmented. (3D Slicer image computing platform | 3D Slicer) Automatic segmentation of skull and cervical spine, as well as skin were performed in dedicated software (LumiNE, Augmedit bv, Netherlands), In this software a visualization scene was automatically deployed including source medical imaging and superimposed 3D segmentation. 12 , 13 The software generates automatically a format viewable with a stereoscopic head up display (HoloLens 2, Microsoft, Richmond, USA). The total active time required for the hologram’s preparation, i.e. the time demanded to perform manual and semi-automatic segmentations since the automatic segmentations did not require any active time, was recorded. Intraoperative hologram use Just before skin disinfection and draping, after patient positioning and a first planning of the skin incision, a manual matching between the hologram, visualized through MxR glasses was performed (Fig. 1 ). Hereby anatomical landmarks (i.e. mandibular angle, sternal notch, external acoustic meatus and glabella) were used as anatomical landmarks for positioning. Anatomical correspondence was verified by the supervising surgeon. The superimposition of the hologram on the surgical situs was utilized by the neurosurgeon to study the position of the carotid bifurcation and its relation to the incision made previously. Then each supervising surgeon was given the opportunity to shorten the surgical incision according to the 3D visualization and each modification was documented. After the usage of the hologram, the operating neurosurgeon was questioned on the impact of the 3D visualization on the anatomical understanding and the use of the MxR system. The interview was performed on the following domains: Usefulness, Ease of Use, Ease of Learning, and Satisfaction. Table 1 describes in more details how the domains mentioned above were defined. Table 1 Definition of the Evaluation Domains Domain Definition Meaning of a high score Ease of Use How naturally users can interact with the MxR system The interface feels straightforward and intuitive Ease of Learning How quickly and comfortably users can get up to speed with the MR tool The system can be mastered by those new to it with little effort Satisfaction How users feel about their overall experience with the MR system The system allows the user to achieve the expected goals for its use. Usefulness How valuable the MR system is, whether it adds meaningful support The technology is seen as genuinely helpful in surgical planning and anatomical understanding. Each domain was given a score from 1, lowest score, to 7, highest score; as score from 5 and above was deemed to be positive 14 . All included neurosurgeons had at least 6 months of exposure to the MxR system and their level of experience in CEA surgery was rated according to the annual number of surgeries performed as experienced (>/= 25 CEA/year as supervising surgeon) and inexperienced 15 . Statistical analysis and comparison with non-MxR CEAs A descriptive analysis was used to analyze the included prospective cohort of patients and characterize the application of MxR on surgical preparation. Data were expressed as percentages, means and standard deviations (SD). All statistical analyses have been performed with Excel 2016 (version 10.0.5491.1000) and R Studio (version 2023.09.0 + 463). Results Demographic and surgical data The study included forty-nine patients with a mean age of 75+/-8 years. The cohort included 28 left (57%) and 21 right (43%) CEAs. Preoperatively, 38 patients (78%) presented symptomatic stenosis. All the patients but one, who demonstrated a NIHSS of 7 points, showed a NIHSS<7, and 43 patients (88%) demonstrated a mRS≤2. After surgery, all patients but one demonstrated no worsening of the scores. Forty-one patients (84%) received a preoperative CTA, 6 patients (12%) an MRA only and 2 patients (4%) underwent both imaging studies. Immediate postoperative imaging control with head and neck CTA was performed for 48 patients (98%), in one patient a doppler-ultrasound was performed instead. All patients showed a successful postoperative result with patent internal carotid artery. Hologram preparation The mean time to achieve complete semi-automatic and manual segmentation was 17+/-6 minutes. While for the majority of the included cases the arterial structures of interest were segmented semi-automatically (38 cases, 76%), the CCA, ICA and ECA were segmented manually in 12 cases (24%). The determination of the level of the bifurcation on the hologram using the level of the vertebral bodies showed that the most represented bifurcation level was between C4 and C5 vertebral body (14 cases, 29%), followed by level C3-C4 (12 cases, 24%). In all cases included in the present cohort, the plaque’s localization included the level of the bifurcation. An overview of the steps of hologram’s preparation is illustrated in Figure 2 . Impact of intraoperative use Mean duration of intra-operative (i.e. during the non-sterile phase of the operation, after positioning and before disinfection and draping), hologram’s use was 5 +/- 2 minutes. Moderate kinking of the affected ICA was observed in 3 cases (6%): In one case (2%), a side-to-side anatomy was reported. Tailoring the skin incision, i.e. shortening it to focus on the position of the bifurcation, based on intraoperative hologram visualization was performed in 16 cases (33%). After being questioned on their experience with MxR, by 3 of the 5 neurosurgeons the mean score of all the domains was above 5. The best scores were given to the domains Ease of Use and Satisfaction, while the worst score was given by an inexperienced surgeon in the domain Usefulness. More details on the results of the interviews are provided in Table 2 . Table 2 : Summary of the interview’s results showing a color-coded representation of the mean values for each domain and a general mean value with standard deviation Illustrative case with ordinary anatomical features A 68-years-old male patient presenting with a transitory ischemic attack (TIA) showed a 50%-stenosis of the right ICA at a Doppler-Ultrasound. A preoperative head and neck CTA documented a carotid bifurcation at C3 vertebral body level and a partially calcified plaque localized at the level of the CCA bifurcation and at the origin of the ICA. Starting from the preoperative CTA as source imaging, a holographic rendering of the plaque and of the CCA, ICA and ECA, as well as the single thyroid artery was performed. After intraoperative patient positioning, the hologram was manually matched with the patient’s head and neck providing a 3D visualization of the carotid bifurcation and plaque, confirming the correct incision planning. The anatomical correctness of the matching of the hologram, the incision planning, the holographic plaque extension and the origin of the thyroid artery was then confirmed intraoperatively after reaching the carotid sheath and opening the CCA and ICA ( Figure 3 ). Illustrative case with complex anatomical features The case of a 78-years-old female patient was presented to the institutional interdisciplinary vascular board to discuss the indication of a left CEA. She presented a fluctuating paresis of the right hemibody as well as right hemodynamic watershed strokes on CT and an 80%-stenosis of the left ICA at Doppler-Ultrasound. The indication of a CEA over a stenting was given, driven by the presence of a floating thrombus at the level of the calcified plaque. The preoperative holographic reconstruction of the anatomy of the patient could demonstrate clearly plaque and thrombus, and it highlighted the presence of a severe kinking (110°) of the ICA distal of the stenosis ( Figure 4 ). Due to the relevant kinking of the ICA and with the aim to correct it surgically, the supervising surgeon decided to remove the plaque using the eversion technique. The eversion of the stenotic left ICA allowed indeed a complete removal of the plaque and a correction of the kinking. In this case, the interactive holographic reconstruction helped by increasing the anatomical appreciation of relevant patient-specific features and endorsed the intraoperative decision to perform the eversion technique. Discussion This study aimed to evaluate the applicability of MxR on surgical planning of CEA and anatomical understanding. In our opinion, the added value of MxR lies in the direct transfer of 2D anatomical details in 3D and the overlay of the 3D reconstruction on the surgical field. This overlay has the potential to enhance the intraoperative identification of relevant morphological details, i.e. height of the bifurcation, loops or kinking, twisted anatomy, as well as the morphology of the plaque and its extension. The impact of an improved intraoperative visualization may be relevant on the effectiveness of the surgical isolation of the carotid sheath and identification of the bifurcation and ICA. The improved anatomical appreciation may be beneficial for less experienced neurosurgeons and but also for expert ones. Less experienced surgeons could profit from the 3D visualization to increase spatial orientation improving their intraoperative understanding. On the other hand, experienced ones may benefit from the clearer depiction of details to further improve and tailor their surgical strategy. Furthermore, the relatively low cost of the system could thereby increase its use for this indication. This study is a first exploration of the effects of the technology and cannot be used to study reduction of complications or improvement of outcome. Despite the wide diffusion of MxR in the neurosurgical field and the presence of multiple studies endorsing the positive impact of this technology on anatomical comprehension, surgical planning and training, to our knowledge no study specific on MxR for CEA planning has been published yet. Preliminary experience on the potential positive impact of this technology on CEA was previously published by our group in a more comprehensive cohort of neurosurgical cases. 5 Neuronavigation technology or ultrasound have not found its way to this procedure because the absence of head fixation and a high cost/benefit ratio. In spite of its merits, the present study has several limitations. First, this study is an initial exploration of the potential benefits of MxR on CEAs and cannot be used to study reduction of complications or improvement of outcome. Furthermore, the nature of the present cohort, including a small number of cases from a tertiary referral center and no control group, may fail to clearly demonstrate the benefits of the application of the technology. A major theoretical limitation of the technology thereby is the absence of rotation in the hologram. Head rotation during operative positioning could provide a change in the intraoperative anatomy compared to the anatomy during scanning which is performed in straight supine position. However, we did not find this of relevant impact for the purposes of this study. Matching was still possible on the combination of anatomical landmarks and the intraoperatively found level of bifurcation was adequate in all cases, although intraoperative hologram-head matching was operator-dependent and the correspondence’s check between hologram and patience anatomy was still subjective. Formal objective measurement of the registration error is therefore a good step for future research. Other intrinsic limitations could also limit its wide adaptation. Its workflow is influenced by the quality of the internet connection, thus, it may not be easy to implement in operating rooms. Also preoperative imaging quality impacts heavily hologram quality. A bad scan will result in an ugly hologram. Future developments should focus primarily on the improvement and automatization of the MxR workflow dedicated to CEA procedures: the head to hologram matching should be made automatic and not operator-dependent, and the hologram should become adaptable to the specific head and neck positioning. Furthermore, in order to increase the reproducibility and applicability of the results, a more numerous and diverse cohort of cases should be examined and matched with a control group. Moreover, the integration of hemodynamic parameters into the holographic rendering, in order to combine patient-specific 3D interactive anatomical information to vessel-specific volume flow rates, flow velocity turbulences and shear stresses should be investigated. MxR could then be integrated in the diagnostic workup for carotid artery stenosis and influence the therapeutic decision making. Another relevant application is the training of surgeons to perform CEAs. MxR could represent a valuable simulation model for CEAs giving the possibility of training different surgical scenarios in a non-threatening environment, and allowing less experienced surgeons to appreciate the nuances and variations of the anatomy of the carotid artery at the neck. This role of MxR should be further explored. Conclusion CEA planning with MxR seems to have an impact on incision planning and preoperative anatomical understanding. Future research should focus on quantification of the benefits in surgical training. Statements and Declarations Funding : the present study was performed as part of the PhD of Dr. med. E. Colombo and received funding through the SURGENT Consortium, University of Zurich (UZH). https://www.hochschulmedizin.uzh.ch/en/projekte/surgent.html Disclosures : Tristan van Doormaal is the Chief Medical Officer of Augmedit, and received a grant from Hanarth foundation, paid to UMC Utrecht. Giuseppe Esposito is a member of the Board of Trustees for the Brain Disease Foundation and is a consultant for Aesculap B. Braun. Luca Regli owns shares of Augmedit. The other authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. References Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke . 2014;45(7):2160-2236. doi:10.1161/STR.0000000000000024 Michalinos A, Chatzimarkos M, Arkadopoulos N, Safioleas M, Troupis T. Anatomical Considerations on Surgical Anatomy of the Carotid Bifurcation. Anat Res Int . 2016;2016:6907472. doi:10.1155/2016/6907472 Alves Ribeiro R, de Souza Ribeiro JA, Omar ARF, Goncalves Caetano A. (PDF) Common Carotid Artery Bifurcation Levels Related to Clinical Relevant Anatomical Landmarks. 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Stroke . 1999;30(9):1751-1758. doi:10.1161/01.str.30.9.1751 Velz J, Esposito G, Wegener S, Kulcsar Z, Luft A, Regli L. [Diagnostic and Therapeutic Management of Carotid Artery Disease]. Praxis (Bern 1994) . 2020;109(9):705-723. doi:10.1024/1661-8157/a003475 Uno M, Takai H, Yagi K, Matsubara S. Surgical Technique for Carotid Endarterectomy: Current Methods and Problems. Neurol Med Chir (Tokyo) . 2020;60(9):419-428. doi:10.2176/nmc.ra.2020-0111 Rothwell PM. Endarterectomy for symptomatic and asymptomatic carotid stenosis. Neurol Clin . 2008;26(4):1079-1097, x. doi:10.1016/j.ncl.2008.09.013 Fode NC, Sundt TM, Robertson JT, Peerless SJ, Shields CB. Multicenter retrospective review of results and complications of carotid endarterectomy in 1981. Stroke . 1986;17(3):370-376. doi:10.1161/01.str.17.3.370 van Doormaal JAM, Fick T, Ali M, Köllen M, van der Kuijp V, van Doormaal TPC. Fully Automatic Adaptive Meshing Based Segmentation of the Ventricular System for Augmented Reality Visualization and Navigation. World Neurosurg . 2021;156:e9-e24. doi:10.1016/j.wneu.2021.07.099 Fick T, van Doormaal JAM, Tosic L, et al. Fully automatic brain tumor segmentation for 3D evaluation in augmented reality. Neurosurg Focus . 2021;51(2):E14. doi:10.3171/2021.5.FOCUS21200 Lund A. Measuring Usability with the USE Questionnaire. ResearchGate . Accessed July 14, 2025. https://www.researchgate.net/publication/230786746_Measuring_Usability_with_the_USE_Questionnaire Breite MD, Breite CN, Sheaffer WW, et al. Carotid endarterectomy surgeon volumes in contemporary practice: A comparison to randomized trial inclusion criteria. Am J Surg . 2021;222(1):241-244. doi:10.1016/j.amjsurg.2020.11.004 Additional Declarations Competing interest reported. Tristan van Doormaal is the Chief Medical Officer of Augmedit, and received a grant from Hanarth foundation, paid to UMC Utrecht. Giuseppe Esposito is a member of the Board of Trustees for the Brain Disease Foundation, and is a consultant for Aesculap B. Braun. Luca Regli owns shares of Augmedit. The other authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 26 Oct, 2025 Reviewers invited by journal 16 Oct, 2025 Editor assigned by journal 03 Oct, 2025 Submission checks completed at journal 03 Oct, 2025 First submitted to journal 26 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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07:08:31","extension":"xml","order_by":29,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":63418,"visible":true,"origin":"","legend":"","description":"","filename":"1cd6e8f7e2e54af88d9e3ea4b0f88f341structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7722134/v1/25b63ba00aee4518c8f9e84c.xml"},{"id":94731514,"identity":"da2fb04c-dbbe-4948-8926-0d7c4c0e5fee","added_by":"auto","created_at":"2025-10-30 07:08:37","extension":"html","order_by":30,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":74264,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7722134/v1/910ac57f2eb29b4eb0104e71.html"},{"id":94731400,"identity":"f6fe764d-dce1-481e-82f7-7b9b046e30f6","added_by":"auto","created_at":"2025-10-30 07:08:32","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":706353,"visible":true,"origin":"","legend":"\u003cp\u003eIllustrative cases showing the identification of the carotid artery bifurcation and its level in correspondence to the cervical vertebra (1a, b and c) and the extent of the plaque (1a, b and c) or the stenosis (1d) after intraoperative hologram-head matching. The bony structures (in white) may be visualized using different transparencies. The calcified parts (Hounsfield Units \u0026gt; 120) of the segmented plaques have been rendered in green, whereas the soft fatty component of the plaque, when visible in the preoperative CTA, were rendered in yellow (1a).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7722134/v1/352827c337bddacd79460520.png"},{"id":94731565,"identity":"b8477b4f-0fe7-4bb1-8b09-c863c88cd4f3","added_by":"auto","created_at":"2025-10-30 07:08:39","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":253556,"visible":true,"origin":"","legend":"\u003cp\u003eSemiautomatic segmentation of the right CCA, ICA and ECA (green), as well as manual plaque segmentation (yellow) on 3D Slicer (2a). Hologram rendering and visualization on LumiNe (2b-c).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7722134/v1/56a86c353256e605c424cdc9.png"},{"id":94731403,"identity":"04e8f58d-69cb-43ea-8ac2-acdc57168da7","added_by":"auto","created_at":"2025-10-30 07:08:32","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":531995,"visible":true,"origin":"","legend":"\u003cp\u003eIntraoperative 3D visualization after patient-positioning, head-hologram matching and surgical incision planning (3a). Intraoperative visualization of the plaque after clamping of the ICA (white star), ECA and thyroid artery (black and white arrow respectively) and CCA (black star) (3b).\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7722134/v1/e41f9cab2bc4847e8f3fcfdf.png"},{"id":94731366,"identity":"624a06ca-12a6-4da6-bc3a-19a4b39bd1e4","added_by":"auto","created_at":"2025-10-30 07:08:26","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":238280,"visible":true,"origin":"","legend":"\u003cp\u003ePreoperative (4a to c) and postoperative (4d) identification of the major pathoanatomical patient-specific features driving surgical planning and intraoperative decisions. Preoperative CTA (4a) and its 3D reconstruction (4b) showing the calcified plaque (red arrow), the thrombus (white triangle) and the kinking (yellow star). The same details visualized and augmented in the holographic reconstruction (4c). The postoperative result (4d).\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7722134/v1/ea6e9198210171706b3da81a.png"},{"id":94827154,"identity":"3196e82e-d710-4fba-88d6-37d9b73a8472","added_by":"auto","created_at":"2025-10-31 06:54:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2642983,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7722134/v1/45eec316-ed18-423b-a118-f376cb4d0028.pdf"}],"financialInterests":"Competing interest reported. Tristan van Doormaal is the Chief Medical Officer of Augmedit, and received a grant from Hanarth foundation, paid to UMC Utrecht. Giuseppe Esposito is a member of the Board of Trustees for the Brain Disease Foundation, and is a consultant for Aesculap B. Braun. Luca Regli owns shares of Augmedit. The other authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.","formattedTitle":"\u003cp\u003eMixed Reality Applied to Surgical Planning and Tailoring of Carotid Endarterectomies\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCarotid endarterectomy (CEA) represents the first line of treatment for high-grade symptomatic and asymptomatic carotid artery stenosis worldwide.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e This surgical procedure has been introduced in the 1950s and has been developed and extensively studied worldwide. The optimal performance of CEA requires experience and training as well as a precise knowledge and understanding of the patient neck anatomy.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe carotid bifurcation lies normally at the level of the vertebral bodies of C3-C4.\u003csup\u003e3\u003c/sup\u003e However this is highly variable and cases of high or low bifurcation must be carefully examined to choose the best therapy (surgery or endovascular, in case of very high or very low carotid location of the plaque).\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003eAlso vessels\u0026rsquo; tortuosity (i.e.: loop or kinking) or anomalies (i.e.: side-by-side carotid) and variations in its branching pattern can occur. Surgeons should take these variations into consideration for surgical planning. However, all these variations may not be adequately projected in three dimensions (3D) by viewing only two-dimensional (2D) imaging.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eMixed Reality (MxR) could be a suitable technology for better 3D visualization and anatomical understanding and could lead to better surgical planning as well as intraoperative visualization of the patient-specific anatomy.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e MxR is a form of Augmented Reality (AR) featured by the overlay of a 3D stereoscopic interactive reconstruction of the patient anatomy, a so-called hologram, over the real world\u0026rsquo;s anatomy using a head mounted display (HMD), thus without losing the perception of the reality around the hologram. This connection substantially augments not only the anatomical appreciation, but also the spatial orientation and comprehension of the anatomical relationships among healthy and pathologic structures.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Therefore, MxR could optimize the surgical planning, increase intraoperative efficiency, decrease intraoperative adverse events and improve surgical outcomes.\u003c/p\u003e\u003cp\u003eThe authors present in this study the experience gathered on MxR application for carotid endarterectomies (CEAs), focusing on the impact on patient-specific anatomical understanding and surgical planning.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e The local review board approved the present study before its performance. All included patients signed an informed consent to give permission to the surgical procedure and to the publication of their clinical and radiological data under general KEK PB_2017_00093/NCT01628406 (Kanton of Zurich Ethical Committee). The present study has been performed in accordance to the principle of the Declaration of Helsinki.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003ePatient clinical and radiological data\u003c/h2\u003e\u003cp\u003eConsecutive patients who underwent CEA surgery planned with MxR between January 2022 and July 2024 at our institution were included in the analysis.\u003c/p\u003e\u003cp\u003eSurgical indication to CEA was given on the basis of ICA stenosis percentage, calculated according to the NASCET criteria, vessel angioanatomy and clinical presentation.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e All the surgical indications were discussed interdisciplinary either at the cerebrovascular board of our Institution (neurologists, neurosurgeons and neurointerventionalists) or case by case. Preoperative and postoperative modified Rankin scale (mRS) and National Institute of Health Stroke Score (NIHSS) were collected for every patient. Each CEA was performed according to the state of art microsurgical technique.\u003csup\u003e\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e Using the preoperative imaging (head and neck CTA and/or MRA), data on plaque presence as well as its position and morphology, carotid bifurcation level (based on cervical vertebral bodies), anatomical variations (side-by-side carotid or abnormal ECA branch origin, i.e. anatomical variations of thyroid artery), carotid vessels\u0026rsquo; tortuosity (kinking and loops) were recorded. Data on postoperative imaging control (CTA) performed within 48 hours from the procedure and postoperative adverse events during the hospital stay were also gathered.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eSegmentation process and hologram preparation\u003c/h3\u003e\n\u003cp\u003eUsing the preoperative radiological studies as source imaging source in the form of Digital Images and Communication in Medicine (DICOM), the CCA, ECA and ICA, as well as the plaques presenting calcifications (when clearly evident) were semi-automatically and manually segmented. (3D Slicer image computing platform | 3D Slicer) Automatic segmentation of skull and cervical spine, as well as skin were performed in dedicated software (LumiNE, Augmedit bv, Netherlands), In this software a visualization scene was automatically deployed including source medical imaging and superimposed 3D segmentation.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e The software generates automatically a format viewable with a stereoscopic head up display (HoloLens 2, Microsoft, Richmond, USA). The total active time required for the hologram\u0026rsquo;s preparation, i.e. the time demanded to perform manual and semi-automatic segmentations since the automatic segmentations did not require any active time, was recorded.\u003c/p\u003e\n\u003ch3\u003eIntraoperative hologram use\u003c/h3\u003e\n\u003cp\u003eJust before skin disinfection and draping, after patient positioning and a first planning of the skin incision, a manual matching between the hologram, visualized through MxR glasses was performed (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Hereby anatomical landmarks (i.e. mandibular angle, sternal notch, external acoustic meatus and glabella) were used as anatomical landmarks for positioning. Anatomical correspondence was verified by the supervising surgeon. The superimposition of the hologram on the surgical situs was utilized by the neurosurgeon to study the position of the carotid bifurcation and its relation to the incision made previously. Then each supervising surgeon was given the opportunity to shorten the surgical incision according to the 3D visualization and each modification was documented. After the usage of the hologram, the operating neurosurgeon was questioned on the impact of the 3D visualization on the anatomical understanding and the use of the MxR system. The interview was performed on the following domains: Usefulness, Ease of Use, Ease of Learning, and Satisfaction. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e describes in more details how the domains mentioned above were defined.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDefinition of the Evaluation Domains\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDomain\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDefinition\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMeaning of a high score\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEase of Use\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHow naturally users can interact with the MxR system\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eThe interface feels straightforward and intuitive\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEase of Learning\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHow quickly and comfortably users can get up to speed with the MR tool\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eThe system can be mastered by those new to it with little effort\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSatisfaction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHow users feel about their overall experience with the MR system\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eThe system allows the user to achieve the expected goals for its use.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUsefulness\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHow valuable the MR system is, whether it adds meaningful support\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eThe technology is seen as genuinely helpful in surgical planning and anatomical understanding.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eEach domain was given a score from 1, lowest score, to 7, highest score; as score from 5 and above was deemed to be positive\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. All included neurosurgeons had at least 6 months of exposure to the MxR system and their level of experience in CEA surgery was rated according to the annual number of surgeries performed as experienced (\u0026gt;/= 25 CEA/year as supervising surgeon) and inexperienced\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n\u003ch3\u003eStatistical analysis and comparison with non-MxR CEAs\u003c/h3\u003e\n\u003cp\u003eA descriptive analysis was used to analyze the included prospective cohort of patients and characterize the application of MxR on surgical preparation. Data were expressed as percentages, means and standard deviations (SD). All statistical analyses have been performed with Excel 2016 (version 10.0.5491.1000) and R Studio (version 2023.09.0\u0026thinsp;+\u0026thinsp;463).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cu\u003eDemographic and surgical data\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe study included forty-nine patients with a mean age of 75+/-8 years. The cohort included 28 left (57%) and 21 right (43%) CEAs.\u003c/p\u003e\n\u003cp\u003ePreoperatively, 38 patients (78%) presented symptomatic stenosis. All the patients but one, who demonstrated a NIHSS of 7 points, showed a NIHSS\u0026lt;7, and 43 patients (88%) demonstrated a mRS\u0026le;2. After surgery, all patients but one demonstrated no worsening of the scores. Forty-one patients (84%) received a preoperative CTA, 6 patients (12%) an MRA only and 2 patients (4%) underwent both imaging studies. Immediate postoperative imaging control with head and neck CTA was performed for 48 patients (98%), in one patient a doppler-ultrasound was performed instead. All patients showed a successful postoperative result with patent internal carotid artery.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eHologram preparation\u0026nbsp;\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe mean time to achieve complete semi-automatic and manual segmentation was 17+/-6 minutes. \u0026nbsp; While for the majority of the included cases the arterial structures of interest were segmented semi-automatically (38 cases, 76%), the CCA, ICA and ECA were segmented manually in 12 cases (24%). The determination of the level of the bifurcation on the hologram using the level of the vertebral bodies showed that the most represented bifurcation level was between C4 and C5 vertebral body (14 cases, 29%), followed by level C3-C4 (12 cases, 24%). In all cases included in the present cohort, the plaque\u0026rsquo;s localization included the level of the bifurcation. An overview of the steps of hologram\u0026rsquo;s preparation is illustrated in \u003cstrong\u003eFigure 2\u003c/strong\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eImpact of intraoperative use\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eMean duration of intra-operative (i.e. during the non-sterile phase of the operation, after positioning and before disinfection and draping), hologram\u0026rsquo;s use was 5 +/- 2 minutes. Moderate kinking of the affected ICA was observed in 3 cases (6%): In one case (2%), a side-to-side anatomy was reported. Tailoring the skin incision, i.e. shortening it to focus on the position of the bifurcation, based on intraoperative hologram visualization was performed in 16 cases (33%).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAfter being questioned on their experience with MxR, by 3 of the 5 neurosurgeons the mean score of all the domains was above 5. The best scores were given to the domains Ease of Use and Satisfaction, while the worst score was given by an inexperienced surgeon in the domain Usefulness. More details on the results of the interviews are provided in \u003cstrong\u003eTable 2\u003c/strong\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eTable 2\u003c/strong\u003e: Summary of the interview\u0026rsquo;s results showing a color-coded representation of the mean values for each domain and a general mean value with standard deviation\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cimg 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\"\u003e\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eIllustrative case with ordinary anatomical features\u0026nbsp;\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eA 68-years-old male patient presenting with a transitory ischemic attack (TIA) showed a 50%-stenosis of the right ICA at a Doppler-Ultrasound. A preoperative head and neck CTA documented a carotid bifurcation at C3 vertebral body level and a partially calcified plaque localized at the level of the CCA bifurcation and at the origin of the ICA. Starting from the preoperative CTA as source imaging, a holographic rendering of the plaque and of the CCA, ICA and ECA, as well as the single thyroid artery was performed. After intraoperative patient positioning, the hologram was manually matched with the patient\u0026rsquo;s head and neck providing a 3D visualization of the carotid bifurcation and plaque, confirming the correct incision planning. The anatomical correctness of the matching of the hologram, the incision planning, the holographic plaque extension and the origin of the thyroid artery was then confirmed intraoperatively after reaching the carotid sheath and opening the CCA and ICA (\u003cstrong\u003eFigure 3\u003c/strong\u003e). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eIllustrative case with complex anatomical features\u0026nbsp;\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe case of a 78-years-old female patient was presented to the institutional interdisciplinary vascular board to discuss the indication of a left CEA. She presented a fluctuating paresis of the right hemibody as well as right hemodynamic watershed strokes on CT and an 80%-stenosis of the left ICA at Doppler-Ultrasound. The indication of a CEA over a stenting was given, driven by the presence of a floating thrombus at the level of the calcified plaque. The preoperative holographic reconstruction of the anatomy of the patient could demonstrate clearly plaque and thrombus, and it highlighted the presence of a severe kinking (110\u0026deg;) of the ICA distal of the stenosis (\u003cstrong\u003eFigure 4\u003c/strong\u003e). Due to the relevant kinking of the ICA and with the aim to correct it surgically, the supervising surgeon decided to remove the plaque using the eversion technique. The eversion of the stenotic left ICA allowed indeed a complete removal of the plaque and a correction of the kinking.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn this case, the interactive holographic reconstruction helped by increasing the anatomical appreciation of relevant patient-specific features and endorsed the intraoperative decision to perform the eversion technique.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study aimed to evaluate the applicability of MxR on surgical planning of CEA and anatomical understanding.\u003c/p\u003e\u003cp\u003eIn our opinion, the added value of MxR lies in the direct transfer of 2D anatomical details in 3D and the overlay of the 3D reconstruction on the surgical field. This overlay has the potential to enhance the intraoperative identification of relevant morphological details, i.e. height of the bifurcation, loops or kinking, twisted anatomy, as well as the morphology of the plaque and its extension. The impact of an improved intraoperative visualization may be relevant on the effectiveness of the surgical isolation of the carotid sheath and identification of the bifurcation and ICA. The improved anatomical appreciation may be beneficial for less experienced neurosurgeons and but also for expert ones. Less experienced surgeons could profit from the 3D visualization to increase spatial orientation improving their intraoperative understanding. On the other hand, experienced ones may benefit from the clearer depiction of details to further improve and tailor their surgical strategy. Furthermore, the relatively low cost of the system could thereby increase its use for this indication. This study is a first exploration of the effects of the technology and cannot be used to study reduction of complications or improvement of outcome.\u003c/p\u003e\u003cp\u003eDespite the wide diffusion of MxR in the neurosurgical field and the presence of multiple studies endorsing the positive impact of this technology on anatomical comprehension, surgical planning and training, to our knowledge no study specific on MxR for CEA planning has been published yet. Preliminary experience on the potential positive impact of this technology on CEA was previously published by our group in a more comprehensive cohort of neurosurgical cases.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Neuronavigation technology or ultrasound have not found its way to this procedure because the absence of head fixation and a high cost/benefit ratio.\u003c/p\u003e\u003cp\u003eIn spite of its merits, the present study has several limitations. First, this study is an initial exploration of the potential benefits of MxR on CEAs and cannot be used to study reduction of complications or improvement of outcome. Furthermore, the nature of the present cohort, including a small number of cases from a tertiary referral center and no control group, may fail to clearly demonstrate the benefits of the application of the technology. A major theoretical limitation of the technology thereby is the absence of rotation in the hologram. Head rotation during operative positioning could provide a change in the intraoperative anatomy compared to the anatomy during scanning which is performed in straight supine position. However, we did not find this of relevant impact for the purposes of this study. Matching was still possible on the combination of anatomical landmarks and the intraoperatively found level of bifurcation was adequate in all cases, although intraoperative hologram-head matching was operator-dependent and the correspondence\u0026rsquo;s check between hologram and patience anatomy was still subjective. Formal objective measurement of the registration error is therefore a good step for future research. Other intrinsic limitations could also limit its wide adaptation. Its workflow is influenced by the quality of the internet connection, thus, it may not be easy to implement in operating rooms. Also preoperative imaging quality impacts heavily hologram quality. A bad scan will result in an ugly hologram.\u003c/p\u003e\u003cp\u003eFuture developments should focus primarily on the improvement and automatization of the MxR workflow dedicated to CEA procedures: the head to hologram matching should be made automatic and not operator-dependent, and the hologram should become adaptable to the specific head and neck positioning. Furthermore, in order to increase the reproducibility and applicability of the results, a more numerous and diverse cohort of cases should be examined and matched with a control group. Moreover, the integration of hemodynamic parameters into the holographic rendering, in order to combine patient-specific 3D interactive anatomical information to vessel-specific volume flow rates, flow velocity turbulences and shear stresses should be investigated. MxR could then be integrated in the diagnostic workup for carotid artery stenosis and influence the therapeutic decision making.\u003c/p\u003e\u003cp\u003eAnother relevant application is the training of surgeons to perform CEAs. MxR could represent a valuable simulation model for CEAs giving the possibility of training different surgical scenarios in a non-threatening environment, and allowing less experienced surgeons to appreciate the nuances and variations of the anatomy of the carotid artery at the neck. This role of MxR should be further explored.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eCEA planning with MxR seems to have an impact on incision planning and preoperative anatomical understanding. Future research should focus on quantification of the benefits in surgical training.\u003c/p\u003e"},{"header":"Statements and Declarations","content":"\u003cp\u003e\u003cu\u003eFunding\u003c/u\u003e: the present study was performed as part of the PhD of Dr. med. E. Colombo and received funding through the SURGENT Consortium, University of Zurich (UZH). https://www.hochschulmedizin.uzh.ch/en/projekte/surgent.html\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eDisclosures\u003c/u\u003e: Tristan van Doormaal is the Chief Medical Officer of Augmedit, and received a grant from Hanarth foundation, paid to UMC Utrecht. Giuseppe Esposito is a member of the Board of Trustees for the Brain Disease Foundation and is a consultant for Aesculap B. Braun. Luca Regli owns shares of Augmedit. The other authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. \u003cem\u003eStroke\u003c/em\u003e. 2014;45(7):2160-2236. doi:10.1161/STR.0000000000000024\u003c/li\u003e\n\u003cli\u003eMichalinos A, Chatzimarkos M, Arkadopoulos N, Safioleas M, Troupis T. Anatomical Considerations on Surgical Anatomy of the Carotid Bifurcation. \u003cem\u003eAnat Res Int\u003c/em\u003e. 2016;2016:6907472. doi:10.1155/2016/6907472\u003c/li\u003e\n\u003cli\u003eAlves Ribeiro R, de Souza Ribeiro JA, Omar ARF, Goncalves Caetano A. (PDF) Common Carotid Artery Bifurcation Levels Related to Clinical Relevant Anatomical Landmarks. \u003cem\u003eInternational Journal of Morphology\u003c/em\u003e. 2006;24(3). doi:10.4067/S0717-95022006000400019\u003c/li\u003e\n\u003cli\u003eSchulz UG, Rothwell PM. Major variation in carotid bifurcation anatomy: a possible risk factor for plaque development? \u003cem\u003eStroke\u003c/em\u003e. 2001;32(11):2522-2529. doi:10.1161/hs1101.097391\u003c/li\u003e\n\u003cli\u003eColombo E, Regli L, Esposito G, et al. Mixed Reality for Cranial Neurosurgical Planning: A Single-Center Applicability Study With the First 107 Subsequent Holograms. \u003cem\u003eOper Neurosurg (Hagerstown)\u003c/em\u003e. 2023;26(5):551-558. doi:10.1227/ons.0000000000001033\u003c/li\u003e\n\u003cli\u003eKos TM, Colombo E, Bartels LW, Robe PA, van Doormaal TPC. Evaluation Metrics for Augmented Reality in Neurosurgical Preoperative Planning, Surgical Navigation, and Surgical Treatment Guidance: A Systematic Review. \u003cem\u003eOper Neurosurg (Hagerstown)\u003c/em\u003e. 2023;26(5):491-501. doi:10.1227/ons.0000000000001009\u003c/li\u003e\n\u003cli\u003eFerguson GG, Eliasziw M, Barr HW, et al. The North American Symptomatic Carotid Endarterectomy Trial : surgical results in 1415 patients. \u003cem\u003eStroke\u003c/em\u003e. 1999;30(9):1751-1758. doi:10.1161/01.str.30.9.1751\u003c/li\u003e\n\u003cli\u003eVelz J, Esposito G, Wegener S, Kulcsar Z, Luft A, Regli L. [Diagnostic and Therapeutic Management of Carotid Artery Disease]. \u003cem\u003ePraxis (Bern 1994)\u003c/em\u003e. 2020;109(9):705-723. doi:10.1024/1661-8157/a003475\u003c/li\u003e\n\u003cli\u003eUno M, Takai H, Yagi K, Matsubara S. Surgical Technique for Carotid Endarterectomy: Current Methods and Problems. \u003cem\u003eNeurol Med Chir (Tokyo)\u003c/em\u003e. 2020;60(9):419-428. doi:10.2176/nmc.ra.2020-0111\u003c/li\u003e\n\u003cli\u003eRothwell PM. Endarterectomy for symptomatic and asymptomatic carotid stenosis. \u003cem\u003eNeurol Clin\u003c/em\u003e. 2008;26(4):1079-1097, x. doi:10.1016/j.ncl.2008.09.013\u003c/li\u003e\n\u003cli\u003eFode NC, Sundt TM, Robertson JT, Peerless SJ, Shields CB. Multicenter retrospective review of results and complications of carotid endarterectomy in 1981. \u003cem\u003eStroke\u003c/em\u003e. 1986;17(3):370-376. doi:10.1161/01.str.17.3.370\u003c/li\u003e\n\u003cli\u003evan Doormaal JAM, Fick T, Ali M, K\u0026ouml;llen M, van der Kuijp V, van Doormaal TPC. Fully Automatic Adaptive Meshing Based Segmentation of the Ventricular System for Augmented Reality Visualization and Navigation. \u003cem\u003eWorld Neurosurg\u003c/em\u003e. 2021;156:e9-e24. doi:10.1016/j.wneu.2021.07.099\u003c/li\u003e\n\u003cli\u003eFick T, van Doormaal JAM, Tosic L, et al. Fully automatic brain tumor segmentation for 3D evaluation in augmented reality. \u003cem\u003eNeurosurg Focus\u003c/em\u003e. 2021;51(2):E14. doi:10.3171/2021.5.FOCUS21200\u003c/li\u003e\n\u003cli\u003eLund A. Measuring Usability with the USE Questionnaire. \u003cem\u003eResearchGate\u003c/em\u003e. Accessed July 14, 2025. https://www.researchgate.net/publication/230786746_Measuring_Usability_with_the_USE_Questionnaire\u003c/li\u003e\n\u003cli\u003eBreite MD, Breite CN, Sheaffer WW, et al. Carotid endarterectomy surgeon volumes in contemporary practice: A comparison to randomized trial inclusion criteria. \u003cem\u003eAm J Surg\u003c/em\u003e. 2021;222(1):241-244. doi:10.1016/j.amjsurg.2020.11.004\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"acta-neurochirurgica","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"anch","sideBox":"Learn more about [Acta Neurochirurgica](http://link.springer.com/journal/701)","snPcode":"701","submissionUrl":"https://submission.springernature.com/new-submission/701/3","title":"Acta Neurochirurgica","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"mixed reality, carotid endarterectomy, surgical revascularization, cerebral ischemia, 3D visualization, surgical planning","lastPublishedDoi":"10.21203/rs.3.rs-7722134/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7722134/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003ePerioperative three-dimensional (3D) anatomical visualization with mixed reality (MxR) may have a relevant impact on adequate carotid endarterectomy (CEA) planning compared to standard imaging studies, by highlighting patient specific anatomical features and allowing the rehearsal of the relevant surgical steps in 3D.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eAll consecutive CEAs planned with MxR between January 2022 and July 2024 were prospectively included. Using the preoperative head and neck CT-angiography (CTA) and/or MR-angiography (MRA), skin, skull, cervical spine and vascular anatomy including plaques were segmented. The resulting 3D interactive hologram was matched on the patient with MxR glasses in the operating room after patient positioning and drawing initial skin incision. The impact of 3D visualization on surgical planning and anatomical understanding was documented and usability testing was performed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eForty-nine CEAs were included. Mean hologram\u0026rsquo;s preparation time was 17+/-8 minutes. Mean duration of intraoperative hologram\u0026rsquo;s use was 5 +/- 2 minutes. The supervising surgeon significantly altered (shortening) the skin incision in 16 cases (33%). Higher scores were given to the domains Ease of Use and Satisfaction.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eCEA planning with MxR seems to have an impact on anatomical understanding for both less experienced neurosurgeons and highly experienced neurosurgeons performing more than 25 CEAs per year. Future research should focus on quantification of the benefits in surgical training and assess the impact on surgical outcomes.\u003c/p\u003e","manuscriptTitle":"Mixed Reality Applied to Surgical Planning and Tailoring of Carotid Endarterectomies","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-30 06:51:02","doi":"10.21203/rs.3.rs-7722134/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"235394508143158021950325507385844022665","date":"2025-10-26T12:06:35+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-16T08:50:31+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-03T11:16:19+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-03T11:04:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"Acta Neurochirurgica","date":"2025-09-26T12:57:52+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"acta-neurochirurgica","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"anch","sideBox":"Learn more about [Acta Neurochirurgica](http://link.springer.com/journal/701)","snPcode":"701","submissionUrl":"https://submission.springernature.com/new-submission/701/3","title":"Acta Neurochirurgica","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"e69f81da-e17b-41ba-ad71-7323b69ac3e2","owner":[],"postedDate":"October 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-06T10:09:47+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-30 06:51:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7722134","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7722134","identity":"rs-7722134","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}