- Email: [email protected]
Intraoperative ultrasound and contrast-enhanced ultrasound in surgical treatment of intramedullary spinal tumors
Journal Pre-proof Intraoperative ultrasound and contrast-enhanced ultrasound in surgical treatment of intramedullary spinal tumors Bo Han, M.D, Dongfang Wu, M.D, Wenqing Jia, M.D., Ph.D, Song Lin, M.D., Ph.D, Yulun Xu, M.D., Ph.D. PII:
S1878-8750(20)30334-X
DOI:
https://doi.org/10.1016/j.wneu.2020.02.059
Reference:
WNEU 14334
To appear in:
World Neurosurgery
Received Date: 19 December 2019 Revised Date:
7 February 2020
Accepted Date: 8 February 2020
Please cite this article as: Han B, Wu D, Jia W, Lin S, Xu Y, Intraoperative ultrasound and contrastenhanced ultrasound in surgical treatment of intramedullary spinal tumors, World Neurosurgery (2020), doi: https://doi.org/10.1016/j.wneu.2020.02.059. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Published by Elsevier Inc.
Original Article Intraoperative ultrasound and contrast-enhanced ultrasound in surgical treatment of intramedullary spinal tumors Bo Hana,b, M.D. Dongfang Wuc, M.D. Wenqing Jiaa,b, M.D., Ph.D. Song Lina,b, M.D., Ph.D. Yulun Xua,b,*, M.D., Ph.D. Affiliations: a
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Fengtai
District, Beijing 100070, China b
China National Clinical Research Center for Neurological Diseases (NCRC-ND), Fengtai
District, Beijing 100070, China c
Department of Ultrasonography, Beijing Tiantan Hospital, Capital Medical University, Fengtai
District, Beijing 100070, China *
Correspondence to: Prof. Yulun Xu, M.D., Ph.D.
Address: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Fengtai District, Beijing 100070, China Email: [email protected]
Running title: Intraoperative ultrasound and intramedullary spinal tumors
Keywords: intraoperative ultrasound; contrast-enhanced ultrasound; spinal tumor; intramedullary tumors; surgical resection
1
Intraoperative ultrasound and contrast-enhanced ultrasound in surgical treatment of intramedullary spinal tumors ABSTRACT BACKGROUND: Surgical resection of intramedullary tumors remains technically challenging. The role of intraoperative ultrasound and contrast-enhanced ultrasound (CEUS) in these surgeries have not yet been well-defined. This study was aimed to evaluate the potential of intraoperative ultrasonography, especially CEUS, in visualizing intramedullary spinal cord tumors, and to assess the values for improving surgical outcomes. METHODS: This prospective study recruited 14 patients with intramedullary spinal cord tumor. All patients underwent tumor resection with intraoperative ultrasound and CEUS. The first ultrasonographic scanning was performed before the dural incision. After the dural incision, a further ultrasonographic scanning was performed over the surface of the spinal cord. During and after the tumor removal, repeated ultrasonographic scanning was conducted to assess the extent of surgical resection. Follow-up data were collected and analyzed. RESULTS: Seven patients had small tumors involving one or two spinal segments, and seven patients showed relatively large tumors involving ≥3 spinal segments. Intraoperatively, ultrasonography was able to visualize the lesion clearly in all of the cases. Using intraoperative ultrasound with CEUS, the tumor boundaries were clearly defined. After an average follow-up period of 15.93 months, the neurological function was improved in 10 (71.4%) cases and remained unchanged in 4 (28.6%) cases; there was no deterioration in individual neurological
2
functions.
CONCLUSIONS: Intraoperative ultrasound is of great value for localizing lesions and determining the extent of dural opening and myelotomy, thus reducing the invasiveness of spinal surgery for intramedullary tumors. CEUS helps to delineate the tumor margins and perfusion features.
3
INTRODUCTION Primary spinal cord tumors comprise 2% to 4% of all neoplasms of the central nervous system (CNS)1. They are anatomically classified into three categories: extradural, intradural extramedullary, and intramedullary. As estimated, intramedullary tumors account for 20%~30% of all primary spinal cord tumors, and these entities can potentially lead to severe neurological deficits, poor quality of life, and even death1. The most common histopathological variants of intramedullary spinal cord tumors are ependymomas, astrocytomas, and hemangioblastomas2. Surgical resection represents the mainstream treatment for intramedullary spinal cord tumors. Although assistive technologies, such as intraoperative electrophysiological monitoring, have been greatly advanced, surgical resection of intramedullary tumors remains technically challenging with considerable risks of neurological injuries3. A precise myelotomy depends on the accurate localization of the intramedullary tumor; nevertheless, in the traditional practice, intraoperative localization is usually determined according to preoperative radiographs and clinicians’ experience. As previously reported, the incidence of mislocalization ranged from 0. 032% to 15%, and blind myelotomy may cause severe neurological deficits4. Additionally, as some intramedullary tumors aggressively invade the spinal cord, the surgical resection margins are difficult to be defined and complete resection may be unattainable. Therefore, a dynamic, real-time, intraoperative imaging tool has great potentials for improving surgical outcomes of intramedullary spinal cord tumors. Currently, intraoperative ultrasound has been sparsely attempted in the spinal surgeries5-9.
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However, the role of intraoperative ultrasound and contrast-enhanced ultrasound (CEUS) have not yet been well-defined and standardized for surgical resection of intramedullary spinal cord tumors10, 11. This study was aimed to evaluate the potential of intraoperative ultrasonography, especially CEUS, in visualizing intramedullary spinal cord tumors, and to assess the values for improving complete resection rate and minimizing surgical trauma.
MATERIALS AND METHODS Patients This prospective study recruited 14 patients with intramedullary spinal cord tumor between January 2018 and June 2018. Intramedullary spinal cord tumor was diagnosed based on preoperative magnetic resonance imaging (MRI). Individual demographic and clinical data were collected. The study was approved by the Institutional Review Board and Ethics Committee of Beijing Tiantan Hospital.
Radiological Evaluation MRI with gadolinium-contrast enhancement was performed as the standard radiological examination pre- and postoperatively in all cases. Using the preoperative MRI, we evaluated the tumor location. Based on perioperative MRI and intraoperative findings, the extent of surgical resection was evaluated.
Intraoperative Ultrasound and CEUS All patients underwent laminotomy and microsurgical resection via the posterior median
5
approach, with intraoperative neurophysiologic monitoring and intraoperative ultrasound with CEUS. Ultrasound sonography was performed using a GE Logiq 5 system (GE Medical Systems, Milwaukee, USA) and an Aloka ProSound Alpha10 system (Aloka, Tokyo, Japan) with a multifrequency (5‐ to 12‐MHz) linear transducer. The real-time images were observed on a monitor. The first ultrasonographic scanning was performed before the dural incision. Briefly, the routine laminotomy was performed with the patient in a lateral-prone position, which allowed an adequate ultrasonographic view of the spinal cord. The operating field was filled with saline solution and the sterile transducer head was gently placed over the dural sac perpendicularly; compression on the dura mater and spinal cord were avoided. Then, we rotated the transducer by 90°, and both longitudinal and axial images were analyzed for evaluating the localization and margins of the tumor and for determining the localization and dimension of the subsequent dural mater incision. After the dural incision, a further ultrasonographic scanning was performed over the surface of the spinal cord. The exact extent of the tumor in height and in transverse diameters was reevaluated. After matching the ultrasonographic images with the preoperative MRI, surgical site and margins of the posterior median myelotomy were designed. During and after the tumor removal, repeated ultrasonographic scanning was conducted to assess the extent of surgical resection.
Prognostic Assessment
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Follow-up data for all patients were obtained during individual office visits, with a mean follow-up time of 15.93 months (standard deviation=1.39, range 13–19). Neurological functions were assessed according to the McCormick classification preoperatively, immediately postoperatively, and during the follow-up12, 13.
RESULTS Clinical Features There were 8 males and 6 females, with an average age of 40.00 ± 12.63 years (range, 22–64 years). The clinical symptoms were focal pain (9/14 cases; 64.3%) and sensorimotor disturbances (13/14; 92.9%) in extremities. The average duration of symptoms from the onset to surgery was 20.14 ± 25.63 months (range, 2–84 months). The clinical characteristics were presented in Table 1.
MRI Characteristics and Intraoperative Findings Based on preoperative MRI, seven patients had small tumors involving one or two spinal segments, and seven patients showed relatively large tumors involving ≥3 spinal segments. Intraoperatively, ultrasonography was able to visualize the lesion clearly in all of the cases. The solid portion of the tumors appeared hyperechoic compared to the normal spinal cord parenchyma and cerebrospinal fluid (CSF), while the intratumoral hemorrhage appeared hypoechoic. The main challenge during the surgical resection of small tumors was accurate localization, as these intramedullary tumors did not alter the morphology of the spinal cord. After opening the
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dura mater, we noted there was no local thickening in the spinal cord, and the location of tumors could not be identified. Using intraoperative ultrasound, the location of these tumors was clearly defined (representative Case No. 1&2 in the following section). Among these small tumors, postoperative histopathology revealed cavernous hemangioma in four cases, astrocytoma in two cases, and ependymoma in one case. The large tumors were poorly demarcated, and the surgical margins were difficult to be determined. Using intraoperative ultrasound with CEUS, the tumor boundaries were clearly defined (representative Case No. 3 in the following section). Among these large tumors, postoperative histopathology showed ependymoma in four cases, astrocytoma in two cases, and anaplastic astrocytoma in one case. With the assistance of intraoperative ultrasound, gross total resection was achieved in all of the cases.
Surgical Outcomes Immediately postoperatively, there was no deterioration in individual neurological functions; the McCormick score was improved in 2 (14.3%) cases and remained unchanged in 12 (85.7%) cases. After an average follow-up period of 15.93 months, the neurological function was improved in 10 (71.4%) cases and remained unchanged in 4 (28.6%) cases.
Illustrative cases Case No. 1: A 39-year-old man presented with a 7-year history of numbness and weakness in
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his legs. One month prior to admission, the symptoms aggravated. Spinal MRI revealed an intramedullary lesion at the T6 level (Figure 1A). A surgical resection was attempted in the local hospital, while the surgeons failed to find the tumor intraoperatively. On this admission, physical examination showed a loss of sensation below the distribution of the T6 dermatome and muscle strength of grade 4/5 in the bilateral lower extremities. Repeated MRI showed the tumor was not removed (Figure 1B). Intraoperatively, ultrasonography demonstrated a mixed-echoic lesion in the axial plane (Figure 1C&D). CEUS showed no enhancement (Figure 1E). In the longitudinal plane, the lesion had a hypoechoic core (Figure 1F). With the assistance of intraoperative ultrasonography, the intramedullary lesion was accurately accessed and completely removed (Figure 1G). After a 16-month follow-up, the neurological function was significantly improved. Case No. 2: A 45-year-old woman presented with a 12-month history of back pain and numbness in her legs. Physical examination showed hypesthesia in the bilateral lower extremities. Spinal MRI revealed a small intramedullary lesion at the T10 level (Figure 2A). Intraoperatively, ultrasonography showed a mixed-echoic lesion with a hypoechoic core (Figure 2B). With the assistance of intraoperative ultrasonography, the lesion was precisely located and gross total resection was achieved. After a 19-month follow-up, the neurological deficits almost recovered. Case No. 3: A 42-year old man presented with an 8-month history of numbness and weakness in his arms and hands. Physical examination showed a loss of sensation and muscle strength of grade 4/5 in the bilateral upper extremities. Spinal MRI showed an intramedullary tumor at the C2-T2 levels (Figure 3A&B). After opening the dura mater, the boundaries of the
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tumor could not be identified (Figure 3C). Ultrasonography demonstrated a hyperechoic tumor (Figure 3D), and CEUS delineated the tumor’s margins clearly (Figure 3E). Based on these findings, we made a precise myelotomy. With repeated ultrasound scanning (Figure 3F), the tumor was gross totally resected (Figure 3G). After a 16-month follow-up, the neurological function was significantly improved.
DISCUSSION Intraoperative ultrasound for visualizing intramedullary spinal cord tumors was firstly reported by Michael H. Reid in 197814. However, in the following decade, its used was not popularized in spinal surgeries due to poor imaging quality and limited surgical field15. With the subsequent advances in ultrasonography devices and techniques, intraoperative ultrasound has been widely attempted to assist the surgical treatment of various spinal diseases, such as spinal tumors10, spinal trauma16, Chiari malformation17, and disc herniation18. In 1991, Epstein et al. proposed that ultrasonography has a specific value for distinguishing the type and extent of the spinal tumor and it greatly facilitates the selection of surgical sites for the myelotomy and tumor resection. Additionally, they suggested the use of intraoperative ultrasound for all intramedullary tumor resections as it can improve postoperative neurological functions19. Although previous studies have reported the application of intraoperative ultrasound in surgical resection of spinal tumors, the definitive value of intraoperative ultrasound, especially CEUS, for localization of intramedullary spinal cord tumors as well as the detailed ultrasonographic characteristics have not yet been well elucidated, and intraoperative ultrasound
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has not been used as a routine auxiliary modality in the spinal surgeries20. Intramedullary spinal cord tumors constitute 2% of all central nervous system tumors. The most common pathological variants are ependymoma, cavernous hemangioma, astrocytoma, and hemangioblastoma20-22. In the current study, we found intraoperative ultrasound could visualize both neoplastic and angiomatous lesions, as long as the echo of the lesion was different from that of the spinal cord parenchyma. However, the clinical application value of intraoperative ultrasound varies for different pathological entities. Cavernous hemangioma, also known as cavernous malformation, is not a true tumor as there is no cellular proliferation, and thus it usually does not cause the local thickening of the spinal cord. Additionally, the majority of spinal cavernous hemangiomas involve only one or two spinal segments. Therefore, intraoperative localization of intramedullary cavernous hemangiomas is always challenging. In our study, as shown in representative case No. 1, the first operation in the local hospital did not find the lesion, and the patient was referred to our department. With the assistance of intraoperative ultrasonography, the cavernous hemangioma was clearly visualized, leading to a precise myelotomy and complete tumor resection. Noteworthily, cavernous hemangiomas are usually angiographically occult23, and consistently, we found cavernous hemangiomas were not enhanced on CEUS. Therefore, the value of CEUS for identification of cavernous hemangiomas may be limited. Ependymoma and astrocytoma occupy approximately 30~40% and 30~45% of all intramedullary spinal cord tumors, respectively24. They are usually poorly demarcated and
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involve multiple spinal segments. The clinical challenge during the surgical resection of these entities is defining the tumor margins, which is pivotal for determining the range of dura mater incision and myelotomy. In our study, intraoperative ultrasonography with CEUS could clearly delineate the contour of ependymomas and astrocytomas. From the above two respective, intraoperative ultrasound is a useful tool for accurately localizing tumors and determining the extent of resection. Additionally, some scholars also proposed that intraoperative ultrasound may have potential values for distinguishing the tumor type, especially for differentiating the solid and cystic components19. In our study, the neoplastic parenchyma appeared hyperechoic, and the cystic portion including the focal hemorrhage showed hypoechoic. Additionally, CEUS provided some information about the perfusion characteristics of intramedullary tumors. Although the definitive diagnosis still needs pathological examinations, certain diagnostic clues can be obtained by individual assessment of combined preoperative MRI and intraoperative ultrasonographic findings. For the clinical application of intraoperative ultrasound in surgical resection of intramedullary spinal cord tumors, we recommend a three-step process as proposed by Maiuri et al.5: 1) the ultrasonographic scanning after the laminotomy and before the dural opening can help to optimize the localization and dimension of the dural mater incision; 2) then, ultrasonographic scanning on the surface of the spinal cord can guide the subsequent myelotomy; 3) during and after the tumor removal, repeated ultrasonographic scanning can facilitate the gross total resection avoiding unnecessary injury to the surrounding spinal cord parenchyma.
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Although intraoperative ultrasound can locate and characterize a lesion accurately and show its relationship to surrounding parenchyma in neurosurgeries, there are some subtle differences between brain surgery and spinal cord surgery. First, intraoperative ultrasound can guide the surgical approach for brain lesions, while myelotomy should only be performed via a posterior median approach to avoid damaging the nerve tracts. Second, tumors affecting the spinal cord are variable in appearance and are not as consistently hyperechoic as most brain tumors25. Intraoperative ultrasonography is critical for defining the spinal cord and the extent of intramedullary lesions, particularly in determining the ventral extension of lesions, which may be invisible to the neurosurgeon’s sight using a posterior laminectomy approach.
CONCLUSIONS Intraoperative ultrasound is of great value for localizing lesions and determining the extent of dural opening and myelotomy, thus reducing the invasiveness of spinal surgery for intramedullary tumors. CEUS helps to delineate the tumor margins and perfusion features. We recommend that intraoperative ultrasound should be used as a routine modality in surgical resection of intramedullary tumors.
ACKNOWLEDGEMENTS We thank all of the patients and their families who trusted us, and all of the physicians and staff members who helped in this study.
Funding
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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
CONFLICT OF INTEREST STATEMENT The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
REFERENCES 1.
Tobin MK, Geraghty JR, Engelhard HH, Linninger AA, Mehta AI. Intramedullary spinal
cord tumors: a review of current and future treatment strategies. Neurosurg Focus. 2015;39(2): E14. https://doi.org/10.3171/2015.5.FOCUS15158. 2.
Liu T, Yang C, Deng X, et al. Clinical characteristics and surgical outcomes of spinal
myxopapillary ependymomas. Neurosurg Rev. 2019. https://doi.org/10.1007/s10143-019-01150-z. 3.
Rashad S, Elwany A, Farhoud A. Surgery for spinal intramedullary tumors: technique,
outcome
and
factors
affecting
resectability.
Neurosurg
Rev.
2018;41(2):
503-511.
https://doi.org/10.1007/s10143-017-0879-z. 4.
Zhang P, Wang G, Sun Z, et al. Application of Multimodal Image Fusion to Precisely
Localize Small Intramedullary Spinal Cord Tumors. World Neurosurg. 2018;118: 246-249. https://doi.org/10.1016/j.wneu.2018.07.034. 5.
Maiuri F, Iaconetta G, de Divitiis O. The role of intraoperative sonography in reducing
invasiveness during surgery for spinal tumors. Minim Invasive Neurosurg. 1997;40(1): 8-12.
14
https://doi.org/10.1055/s-2008-1053405. 6.
Toktas ZO, Sahin S, Koban O, Sorar M, Konya D. Is intraoperative ultrasound required in
cervical spinal tumors? A prospective study. Turk Neurosurg. 2013;23(5): 600-606. https://doi.org/10.5137/1019-5149.JTN.7199-12.1. 7.
Haciyakupoglu E, Yuvruk E, Onen MR, Naderi S. The Use of Intraoperative
Ultrasonography in Intradural Spinal Tumor Surgery. Turk Neurosurg. 2019;29(2): 237-241. https://doi.org/10.5137/1019-5149.JTN.23296-18.3. 8.
Prada F, Vetrano IG, Filippini A, et al. Intraoperative ultrasound in spinal tumor surgery. J
Ultrasound. 2014;17(3): 195-202. https://doi.org/10.1007/s40477-014-0102-9. 9.
Vasudeva VS, Abd-El-Barr M, Pompeu YA, Karhade A, Groff MW, Lu Y. Use of
Intraoperative Ultrasound During Spinal Surgery. Global Spine J. 2017;7(7): 648-656. https://doi.org/10.1177/2192568217700100. 10. Vetrano IG, Prada F, Nataloni IF, Bene MD, Dimeco F, Valentini LG. Discrete or diffuse intramedullary tumor? Contrast-enhanced intraoperative ultrasound in a case of intramedullary cervicothoracic hemangioblastomas mimicking a diffuse infiltrative glioma: technical note and case report. Neurosurg Focus. 2015;39(2): E17. https://doi.org/10.3171/2015.5.FOCUS15162. 11. Prada F, Vetrano IG, DiMeco F. Contrast-enhanced ultrasound (CEUS) in spinal tumor surgery.
Acta
Neurochir
(Wien).
2018;160(9):
1869-1871.
https://doi.org/10.1007/s00701-018-3626-5. 12. Aghakhani N, David P, Parker F, Lacroix C, Benoudiba F, Tadie M. Intramedullary spinal
15
ependymomas: analysis of a consecutive series of 82 adult cases with particular attention to patients with no preoperative neurological deficit. Neurosurgery. 2008;62(6): 1279-1285; discussion 1285-1276. https://doi.org/10.1227/01.neu.0000333299.26566.15. 13. McCormick PC, Torres R, Post KD, Stein BM. Intramedullary ependymoma of the spinal cord. J Neurosurg. 1990;72(4): 523-532. https://doi.org/10.3171/jns.1990.72.4.0523. 14. Reid MH. Ultrasonic visualization of a cervical cord cystic astrocytoma. AJR Am J Roentgenol. 1978;131(5): 907-908. https://doi.org/10.2214/ajr.131.5.907. 15. Ganau M, Syrmos N, Martin AR, Jiang F, Fehlings MG. Intraoperative ultrasound in spine surgery: history, current applications, future developments. Quant Imaging Med Surg. 2018;8(3): 261-267. https://doi.org/10.21037/qims.2018.04.02. 16. Khaing ZZ, Cates LN, DeWees DM, et al. Contrast-enhanced ultrasound to visualize hemodynamic changes after rodent spinal cord injury. J Neurosurg Spine. 2018;29(3): 306-313. https://doi.org/10.3171/2018.1.SPINE171202. 17. Deng X, Yang C, Gan J, et al. Long-term outcomes after small-bone-window posterior fossa decompression and duraplasty in adults with Chiari malformation type I. World neurosurgery. 2015;84(4): 998-1004. 18. Neale N, Ramayya A, Welch W. Surgical Management of Idiopathic Thoracic Spinal Cord Herniation. World Neurosurg. 2019;129: 81-84. https://doi.org/10.1016/j.wneu.2019.05.219. 19. Epstein FJ, Farmer JP, Schneider SJ. Intraoperative ultrasonography: an important surgical adjunct
for
intramedullary
tumors.
J
Neurosurg.
1991;74(5):
729-733.
16
https://doi.org/10.3171/jns.1991.74.5.0729. 20. Zhou H, Miller D, Schulte DM, et al. Intraoperative ultrasound assistance in treatment of intradural
spinal
tumours.
Clin
Neurol
Neurosurg.
2011;113(7):
531-537.
https://doi.org/10.1016/j.clineuro.2011.03.006. 21. Yang C, Li G, Fang J, et al. Intramedullary gangliogliomas: clinical features, surgical outcomes, and neuropathic scoliosis. Journal of neuro-oncology. 2014;116(1): 135-143. 22. Deng X, Wang K, Wu L, et al. Intraspinal hemangioblastomas: analysis of 92 cases in a single institution. Journal of Neurosurgery: Spine. 2014;21(2): 260-269. 23. Clark AJ, Wang DD, Lawton MT. Spinal cavernous malformations. Handbook of clinical neurology. Vol 143. Elsevier; 2017:303-308. 24. Regelsberger J, Fritzsche E, Langer N, Westphal M. Intraoperative sonography of intra- and extramedullary
tumors.
Ultrasound
Med
Biol.
2005;31(5):
593-598.
https://doi.org/10.1016/j.ultrasmedbio.2005.01.016. 25. Kane RA, Kruskal JB. Intraoperative ultrasonography of the brain and spine. Ultrasound Q. 2007;23(1): 23-39. http://doi.org/10.1097/01.ruq.0000263840.92560.72.
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FIGURE LEGENDS Figure 1. Clinical and radiological profiles of Case No. 1 (A) Spinal MRI in the local hospital revealed an intramedullary lesion (arrow) at the T6 level. (B) On this admission, spinal MRI showed the tumor (arrow) was not removed in the prior operation. (C&D) Intraoperative ultrasonography demonstrated a mixed-echoic lesion (arrows) in the axial plane. (E) CEUS showed the lesion was not enhanced. (F) In the longitudinal plane, the lesion (arrows) had a hypoechoic core. (G) With the assistance of intraoperative ultrasonography, the intramedullary lesion (arrow) was accurately localized and completely removed.
Figure 2. Radiological profiles of Case No. 2 (A) Preoperative spinal MRI revealed a small intramedullary lesion (arrow) at the T10 level. (B) Intraoperative ultrasonography showed a mixed-echoic lesion (arrows) with a hypoechoic core.
Figure 3. Clinical and radiological profiles of Case No. 3 (A&B) Preoperative spinal MRI showed an intramedullary tumor (arrow) at the C2-T2 levels. (C) After opening the dura mater, the boundaries of the tumor could not be identified. (D) Ultrasonography demonstrated a hyperechoic tumor (arrows). (E) CEUS delineated the tumor’s margins clearly (arrows). (F) Repeated ultrasound scans were performed during the tumor resection. (G) Eventually, the tumor was gross totally resected.
Table 1. Clinical profiles of the patients with intramedullary spinal lesions Case Gender Age Symptoms Duration Location No. (years) (months) of lesion 1 Male 39 Lower-extremity numbness 84 T6 and weakness 2 Female 45 Back pain, lower-extremity 12 T10 numbness 3 Male 42 Upper-extremity numbness 8 C2-T2 and weakness 4 Female 49 Back pain, upper-extremity 24 C4-C6 numbness 5 Female 28 Back pain, lower-extremity 6 C5-T2 numbness and weakness 6 Female 50 Back pain, lower-extremity 8 T12 weakness 7 Male 24 Back pain, lower-extremity 2 T7-T10 weakness 8 Female 29 Back pain, lower-extremity 2 T10-T11 numbness and weakness 9 Male 22 Back pain, right-extremity 2 T1-T2 numbness 10 Male 40 Lower-extremity numbness 6 C5-T2 11 Male 57 Back pain 60 T12-L3 12 Male 28 Upper-extremity numbness 2 C1-C5 and weakness 13 Male 64 Upper-extremity numbness 18 C6-C7 and weakness 14 Female 43 Neck pain, four-extremity 48 C1-C2 numbness Pre-op, pre-operative; Post-op, postoperative
Pathology Cavernous hemangioma Cavernous hemangioma Ependymoma
Follow-up (months) 16
McCormick Grading Pre-op Post-op Follow-up III III II
19
II
II
I
16
III
III
II
Astrocytoma
16
II
II
I
Ependymoma
16
IV
IV
IV
Astrocytoma
16
III
III
II
Astrocytoma
15
III
II
I
Cavernous hemangioma Cavernous hemangioma Ependymoma Ependymoma Anaplastic astrocytoma Astrocytoma
14
III
III
III
13
II
I
I
17 17 16
II I III
II I III
I I III
16
III
III
I
16
II
II
I
Ependymoma
HIGHLIGHTS： ：
Surgical resection of intramedullary tumors remains technically challenging.
Intraoperative ultrasound is of great value for localizing lesions.
Intraoperative ultrasound helps determining the extent of spinal surgery.
Intraoperative ultrasound reduces the invasiveness of spinal surgery.
ABBREVIATIONS LIST： ： CEUS: contrast-enhanced ultrasound CNS: central nervous system MRI: magnetic resonance imaging CSF: cerebrospinal fluid
CRediT author statement Bo Han: Conceptualization, Methodology, Writing-Original draft preparation. Dongfang Wu: Data collection and analysis, Software. Wenqing Jia: Visualization, Investigation. Song Lin: Data collection. Yulun Xu: Supervision, Writing-Reviewing and Editing,
S1878-8750(20)30334-X
DOI:
https://doi.org/10.1016/j.wneu.2020.02.059
Reference:
WNEU 14334
To appear in:
World Neurosurgery
Received Date: 19 December 2019 Revised Date:
7 February 2020
Accepted Date: 8 February 2020
Please cite this article as: Han B, Wu D, Jia W, Lin S, Xu Y, Intraoperative ultrasound and contrastenhanced ultrasound in surgical treatment of intramedullary spinal tumors, World Neurosurgery (2020), doi: https://doi.org/10.1016/j.wneu.2020.02.059. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Published by Elsevier Inc.
Original Article Intraoperative ultrasound and contrast-enhanced ultrasound in surgical treatment of intramedullary spinal tumors Bo Hana,b, M.D. Dongfang Wuc, M.D. Wenqing Jiaa,b, M.D., Ph.D. Song Lina,b, M.D., Ph.D. Yulun Xua,b,*, M.D., Ph.D. Affiliations: a
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Fengtai
District, Beijing 100070, China b
China National Clinical Research Center for Neurological Diseases (NCRC-ND), Fengtai
District, Beijing 100070, China c
Department of Ultrasonography, Beijing Tiantan Hospital, Capital Medical University, Fengtai
District, Beijing 100070, China *
Correspondence to: Prof. Yulun Xu, M.D., Ph.D.
Address: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Fengtai District, Beijing 100070, China Email: [email protected]
Running title: Intraoperative ultrasound and intramedullary spinal tumors
Keywords: intraoperative ultrasound; contrast-enhanced ultrasound; spinal tumor; intramedullary tumors; surgical resection
1
Intraoperative ultrasound and contrast-enhanced ultrasound in surgical treatment of intramedullary spinal tumors ABSTRACT BACKGROUND: Surgical resection of intramedullary tumors remains technically challenging. The role of intraoperative ultrasound and contrast-enhanced ultrasound (CEUS) in these surgeries have not yet been well-defined. This study was aimed to evaluate the potential of intraoperative ultrasonography, especially CEUS, in visualizing intramedullary spinal cord tumors, and to assess the values for improving surgical outcomes. METHODS: This prospective study recruited 14 patients with intramedullary spinal cord tumor. All patients underwent tumor resection with intraoperative ultrasound and CEUS. The first ultrasonographic scanning was performed before the dural incision. After the dural incision, a further ultrasonographic scanning was performed over the surface of the spinal cord. During and after the tumor removal, repeated ultrasonographic scanning was conducted to assess the extent of surgical resection. Follow-up data were collected and analyzed. RESULTS: Seven patients had small tumors involving one or two spinal segments, and seven patients showed relatively large tumors involving ≥3 spinal segments. Intraoperatively, ultrasonography was able to visualize the lesion clearly in all of the cases. Using intraoperative ultrasound with CEUS, the tumor boundaries were clearly defined. After an average follow-up period of 15.93 months, the neurological function was improved in 10 (71.4%) cases and remained unchanged in 4 (28.6%) cases; there was no deterioration in individual neurological
2
functions.
CONCLUSIONS: Intraoperative ultrasound is of great value for localizing lesions and determining the extent of dural opening and myelotomy, thus reducing the invasiveness of spinal surgery for intramedullary tumors. CEUS helps to delineate the tumor margins and perfusion features.
3
INTRODUCTION Primary spinal cord tumors comprise 2% to 4% of all neoplasms of the central nervous system (CNS)1. They are anatomically classified into three categories: extradural, intradural extramedullary, and intramedullary. As estimated, intramedullary tumors account for 20%~30% of all primary spinal cord tumors, and these entities can potentially lead to severe neurological deficits, poor quality of life, and even death1. The most common histopathological variants of intramedullary spinal cord tumors are ependymomas, astrocytomas, and hemangioblastomas2. Surgical resection represents the mainstream treatment for intramedullary spinal cord tumors. Although assistive technologies, such as intraoperative electrophysiological monitoring, have been greatly advanced, surgical resection of intramedullary tumors remains technically challenging with considerable risks of neurological injuries3. A precise myelotomy depends on the accurate localization of the intramedullary tumor; nevertheless, in the traditional practice, intraoperative localization is usually determined according to preoperative radiographs and clinicians’ experience. As previously reported, the incidence of mislocalization ranged from 0. 032% to 15%, and blind myelotomy may cause severe neurological deficits4. Additionally, as some intramedullary tumors aggressively invade the spinal cord, the surgical resection margins are difficult to be defined and complete resection may be unattainable. Therefore, a dynamic, real-time, intraoperative imaging tool has great potentials for improving surgical outcomes of intramedullary spinal cord tumors. Currently, intraoperative ultrasound has been sparsely attempted in the spinal surgeries5-9.
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However, the role of intraoperative ultrasound and contrast-enhanced ultrasound (CEUS) have not yet been well-defined and standardized for surgical resection of intramedullary spinal cord tumors10, 11. This study was aimed to evaluate the potential of intraoperative ultrasonography, especially CEUS, in visualizing intramedullary spinal cord tumors, and to assess the values for improving complete resection rate and minimizing surgical trauma.
MATERIALS AND METHODS Patients This prospective study recruited 14 patients with intramedullary spinal cord tumor between January 2018 and June 2018. Intramedullary spinal cord tumor was diagnosed based on preoperative magnetic resonance imaging (MRI). Individual demographic and clinical data were collected. The study was approved by the Institutional Review Board and Ethics Committee of Beijing Tiantan Hospital.
Radiological Evaluation MRI with gadolinium-contrast enhancement was performed as the standard radiological examination pre- and postoperatively in all cases. Using the preoperative MRI, we evaluated the tumor location. Based on perioperative MRI and intraoperative findings, the extent of surgical resection was evaluated.
Intraoperative Ultrasound and CEUS All patients underwent laminotomy and microsurgical resection via the posterior median
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approach, with intraoperative neurophysiologic monitoring and intraoperative ultrasound with CEUS. Ultrasound sonography was performed using a GE Logiq 5 system (GE Medical Systems, Milwaukee, USA) and an Aloka ProSound Alpha10 system (Aloka, Tokyo, Japan) with a multifrequency (5‐ to 12‐MHz) linear transducer. The real-time images were observed on a monitor. The first ultrasonographic scanning was performed before the dural incision. Briefly, the routine laminotomy was performed with the patient in a lateral-prone position, which allowed an adequate ultrasonographic view of the spinal cord. The operating field was filled with saline solution and the sterile transducer head was gently placed over the dural sac perpendicularly; compression on the dura mater and spinal cord were avoided. Then, we rotated the transducer by 90°, and both longitudinal and axial images were analyzed for evaluating the localization and margins of the tumor and for determining the localization and dimension of the subsequent dural mater incision. After the dural incision, a further ultrasonographic scanning was performed over the surface of the spinal cord. The exact extent of the tumor in height and in transverse diameters was reevaluated. After matching the ultrasonographic images with the preoperative MRI, surgical site and margins of the posterior median myelotomy were designed. During and after the tumor removal, repeated ultrasonographic scanning was conducted to assess the extent of surgical resection.
Prognostic Assessment
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Follow-up data for all patients were obtained during individual office visits, with a mean follow-up time of 15.93 months (standard deviation=1.39, range 13–19). Neurological functions were assessed according to the McCormick classification preoperatively, immediately postoperatively, and during the follow-up12, 13.
RESULTS Clinical Features There were 8 males and 6 females, with an average age of 40.00 ± 12.63 years (range, 22–64 years). The clinical symptoms were focal pain (9/14 cases; 64.3%) and sensorimotor disturbances (13/14; 92.9%) in extremities. The average duration of symptoms from the onset to surgery was 20.14 ± 25.63 months (range, 2–84 months). The clinical characteristics were presented in Table 1.
MRI Characteristics and Intraoperative Findings Based on preoperative MRI, seven patients had small tumors involving one or two spinal segments, and seven patients showed relatively large tumors involving ≥3 spinal segments. Intraoperatively, ultrasonography was able to visualize the lesion clearly in all of the cases. The solid portion of the tumors appeared hyperechoic compared to the normal spinal cord parenchyma and cerebrospinal fluid (CSF), while the intratumoral hemorrhage appeared hypoechoic. The main challenge during the surgical resection of small tumors was accurate localization, as these intramedullary tumors did not alter the morphology of the spinal cord. After opening the
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dura mater, we noted there was no local thickening in the spinal cord, and the location of tumors could not be identified. Using intraoperative ultrasound, the location of these tumors was clearly defined (representative Case No. 1&2 in the following section). Among these small tumors, postoperative histopathology revealed cavernous hemangioma in four cases, astrocytoma in two cases, and ependymoma in one case. The large tumors were poorly demarcated, and the surgical margins were difficult to be determined. Using intraoperative ultrasound with CEUS, the tumor boundaries were clearly defined (representative Case No. 3 in the following section). Among these large tumors, postoperative histopathology showed ependymoma in four cases, astrocytoma in two cases, and anaplastic astrocytoma in one case. With the assistance of intraoperative ultrasound, gross total resection was achieved in all of the cases.
Surgical Outcomes Immediately postoperatively, there was no deterioration in individual neurological functions; the McCormick score was improved in 2 (14.3%) cases and remained unchanged in 12 (85.7%) cases. After an average follow-up period of 15.93 months, the neurological function was improved in 10 (71.4%) cases and remained unchanged in 4 (28.6%) cases.
Illustrative cases Case No. 1: A 39-year-old man presented with a 7-year history of numbness and weakness in
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his legs. One month prior to admission, the symptoms aggravated. Spinal MRI revealed an intramedullary lesion at the T6 level (Figure 1A). A surgical resection was attempted in the local hospital, while the surgeons failed to find the tumor intraoperatively. On this admission, physical examination showed a loss of sensation below the distribution of the T6 dermatome and muscle strength of grade 4/5 in the bilateral lower extremities. Repeated MRI showed the tumor was not removed (Figure 1B). Intraoperatively, ultrasonography demonstrated a mixed-echoic lesion in the axial plane (Figure 1C&D). CEUS showed no enhancement (Figure 1E). In the longitudinal plane, the lesion had a hypoechoic core (Figure 1F). With the assistance of intraoperative ultrasonography, the intramedullary lesion was accurately accessed and completely removed (Figure 1G). After a 16-month follow-up, the neurological function was significantly improved. Case No. 2: A 45-year-old woman presented with a 12-month history of back pain and numbness in her legs. Physical examination showed hypesthesia in the bilateral lower extremities. Spinal MRI revealed a small intramedullary lesion at the T10 level (Figure 2A). Intraoperatively, ultrasonography showed a mixed-echoic lesion with a hypoechoic core (Figure 2B). With the assistance of intraoperative ultrasonography, the lesion was precisely located and gross total resection was achieved. After a 19-month follow-up, the neurological deficits almost recovered. Case No. 3: A 42-year old man presented with an 8-month history of numbness and weakness in his arms and hands. Physical examination showed a loss of sensation and muscle strength of grade 4/5 in the bilateral upper extremities. Spinal MRI showed an intramedullary tumor at the C2-T2 levels (Figure 3A&B). After opening the dura mater, the boundaries of the
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tumor could not be identified (Figure 3C). Ultrasonography demonstrated a hyperechoic tumor (Figure 3D), and CEUS delineated the tumor’s margins clearly (Figure 3E). Based on these findings, we made a precise myelotomy. With repeated ultrasound scanning (Figure 3F), the tumor was gross totally resected (Figure 3G). After a 16-month follow-up, the neurological function was significantly improved.
DISCUSSION Intraoperative ultrasound for visualizing intramedullary spinal cord tumors was firstly reported by Michael H. Reid in 197814. However, in the following decade, its used was not popularized in spinal surgeries due to poor imaging quality and limited surgical field15. With the subsequent advances in ultrasonography devices and techniques, intraoperative ultrasound has been widely attempted to assist the surgical treatment of various spinal diseases, such as spinal tumors10, spinal trauma16, Chiari malformation17, and disc herniation18. In 1991, Epstein et al. proposed that ultrasonography has a specific value for distinguishing the type and extent of the spinal tumor and it greatly facilitates the selection of surgical sites for the myelotomy and tumor resection. Additionally, they suggested the use of intraoperative ultrasound for all intramedullary tumor resections as it can improve postoperative neurological functions19. Although previous studies have reported the application of intraoperative ultrasound in surgical resection of spinal tumors, the definitive value of intraoperative ultrasound, especially CEUS, for localization of intramedullary spinal cord tumors as well as the detailed ultrasonographic characteristics have not yet been well elucidated, and intraoperative ultrasound
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has not been used as a routine auxiliary modality in the spinal surgeries20. Intramedullary spinal cord tumors constitute 2% of all central nervous system tumors. The most common pathological variants are ependymoma, cavernous hemangioma, astrocytoma, and hemangioblastoma20-22. In the current study, we found intraoperative ultrasound could visualize both neoplastic and angiomatous lesions, as long as the echo of the lesion was different from that of the spinal cord parenchyma. However, the clinical application value of intraoperative ultrasound varies for different pathological entities. Cavernous hemangioma, also known as cavernous malformation, is not a true tumor as there is no cellular proliferation, and thus it usually does not cause the local thickening of the spinal cord. Additionally, the majority of spinal cavernous hemangiomas involve only one or two spinal segments. Therefore, intraoperative localization of intramedullary cavernous hemangiomas is always challenging. In our study, as shown in representative case No. 1, the first operation in the local hospital did not find the lesion, and the patient was referred to our department. With the assistance of intraoperative ultrasonography, the cavernous hemangioma was clearly visualized, leading to a precise myelotomy and complete tumor resection. Noteworthily, cavernous hemangiomas are usually angiographically occult23, and consistently, we found cavernous hemangiomas were not enhanced on CEUS. Therefore, the value of CEUS for identification of cavernous hemangiomas may be limited. Ependymoma and astrocytoma occupy approximately 30~40% and 30~45% of all intramedullary spinal cord tumors, respectively24. They are usually poorly demarcated and
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involve multiple spinal segments. The clinical challenge during the surgical resection of these entities is defining the tumor margins, which is pivotal for determining the range of dura mater incision and myelotomy. In our study, intraoperative ultrasonography with CEUS could clearly delineate the contour of ependymomas and astrocytomas. From the above two respective, intraoperative ultrasound is a useful tool for accurately localizing tumors and determining the extent of resection. Additionally, some scholars also proposed that intraoperative ultrasound may have potential values for distinguishing the tumor type, especially for differentiating the solid and cystic components19. In our study, the neoplastic parenchyma appeared hyperechoic, and the cystic portion including the focal hemorrhage showed hypoechoic. Additionally, CEUS provided some information about the perfusion characteristics of intramedullary tumors. Although the definitive diagnosis still needs pathological examinations, certain diagnostic clues can be obtained by individual assessment of combined preoperative MRI and intraoperative ultrasonographic findings. For the clinical application of intraoperative ultrasound in surgical resection of intramedullary spinal cord tumors, we recommend a three-step process as proposed by Maiuri et al.5: 1) the ultrasonographic scanning after the laminotomy and before the dural opening can help to optimize the localization and dimension of the dural mater incision; 2) then, ultrasonographic scanning on the surface of the spinal cord can guide the subsequent myelotomy; 3) during and after the tumor removal, repeated ultrasonographic scanning can facilitate the gross total resection avoiding unnecessary injury to the surrounding spinal cord parenchyma.
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Although intraoperative ultrasound can locate and characterize a lesion accurately and show its relationship to surrounding parenchyma in neurosurgeries, there are some subtle differences between brain surgery and spinal cord surgery. First, intraoperative ultrasound can guide the surgical approach for brain lesions, while myelotomy should only be performed via a posterior median approach to avoid damaging the nerve tracts. Second, tumors affecting the spinal cord are variable in appearance and are not as consistently hyperechoic as most brain tumors25. Intraoperative ultrasonography is critical for defining the spinal cord and the extent of intramedullary lesions, particularly in determining the ventral extension of lesions, which may be invisible to the neurosurgeon’s sight using a posterior laminectomy approach.
CONCLUSIONS Intraoperative ultrasound is of great value for localizing lesions and determining the extent of dural opening and myelotomy, thus reducing the invasiveness of spinal surgery for intramedullary tumors. CEUS helps to delineate the tumor margins and perfusion features. We recommend that intraoperative ultrasound should be used as a routine modality in surgical resection of intramedullary tumors.
ACKNOWLEDGEMENTS We thank all of the patients and their families who trusted us, and all of the physicians and staff members who helped in this study.
Funding
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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
CONFLICT OF INTEREST STATEMENT The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
REFERENCES 1.
Tobin MK, Geraghty JR, Engelhard HH, Linninger AA, Mehta AI. Intramedullary spinal
cord tumors: a review of current and future treatment strategies. Neurosurg Focus. 2015;39(2): E14. https://doi.org/10.3171/2015.5.FOCUS15158. 2.
Liu T, Yang C, Deng X, et al. Clinical characteristics and surgical outcomes of spinal
myxopapillary ependymomas. Neurosurg Rev. 2019. https://doi.org/10.1007/s10143-019-01150-z. 3.
Rashad S, Elwany A, Farhoud A. Surgery for spinal intramedullary tumors: technique,
outcome
and
factors
affecting
resectability.
Neurosurg
Rev.
2018;41(2):
503-511.
https://doi.org/10.1007/s10143-017-0879-z. 4.
Zhang P, Wang G, Sun Z, et al. Application of Multimodal Image Fusion to Precisely
Localize Small Intramedullary Spinal Cord Tumors. World Neurosurg. 2018;118: 246-249. https://doi.org/10.1016/j.wneu.2018.07.034. 5.
Maiuri F, Iaconetta G, de Divitiis O. The role of intraoperative sonography in reducing
invasiveness during surgery for spinal tumors. Minim Invasive Neurosurg. 1997;40(1): 8-12.
14
https://doi.org/10.1055/s-2008-1053405. 6.
Toktas ZO, Sahin S, Koban O, Sorar M, Konya D. Is intraoperative ultrasound required in
cervical spinal tumors? A prospective study. Turk Neurosurg. 2013;23(5): 600-606. https://doi.org/10.5137/1019-5149.JTN.7199-12.1. 7.
Haciyakupoglu E, Yuvruk E, Onen MR, Naderi S. The Use of Intraoperative
Ultrasonography in Intradural Spinal Tumor Surgery. Turk Neurosurg. 2019;29(2): 237-241. https://doi.org/10.5137/1019-5149.JTN.23296-18.3. 8.
Prada F, Vetrano IG, Filippini A, et al. Intraoperative ultrasound in spinal tumor surgery. J
Ultrasound. 2014;17(3): 195-202. https://doi.org/10.1007/s40477-014-0102-9. 9.
Vasudeva VS, Abd-El-Barr M, Pompeu YA, Karhade A, Groff MW, Lu Y. Use of
Intraoperative Ultrasound During Spinal Surgery. Global Spine J. 2017;7(7): 648-656. https://doi.org/10.1177/2192568217700100. 10. Vetrano IG, Prada F, Nataloni IF, Bene MD, Dimeco F, Valentini LG. Discrete or diffuse intramedullary tumor? Contrast-enhanced intraoperative ultrasound in a case of intramedullary cervicothoracic hemangioblastomas mimicking a diffuse infiltrative glioma: technical note and case report. Neurosurg Focus. 2015;39(2): E17. https://doi.org/10.3171/2015.5.FOCUS15162. 11. Prada F, Vetrano IG, DiMeco F. Contrast-enhanced ultrasound (CEUS) in spinal tumor surgery.
Acta
Neurochir
(Wien).
2018;160(9):
1869-1871.
https://doi.org/10.1007/s00701-018-3626-5. 12. Aghakhani N, David P, Parker F, Lacroix C, Benoudiba F, Tadie M. Intramedullary spinal
15
ependymomas: analysis of a consecutive series of 82 adult cases with particular attention to patients with no preoperative neurological deficit. Neurosurgery. 2008;62(6): 1279-1285; discussion 1285-1276. https://doi.org/10.1227/01.neu.0000333299.26566.15. 13. McCormick PC, Torres R, Post KD, Stein BM. Intramedullary ependymoma of the spinal cord. J Neurosurg. 1990;72(4): 523-532. https://doi.org/10.3171/jns.1990.72.4.0523. 14. Reid MH. Ultrasonic visualization of a cervical cord cystic astrocytoma. AJR Am J Roentgenol. 1978;131(5): 907-908. https://doi.org/10.2214/ajr.131.5.907. 15. Ganau M, Syrmos N, Martin AR, Jiang F, Fehlings MG. Intraoperative ultrasound in spine surgery: history, current applications, future developments. Quant Imaging Med Surg. 2018;8(3): 261-267. https://doi.org/10.21037/qims.2018.04.02. 16. Khaing ZZ, Cates LN, DeWees DM, et al. Contrast-enhanced ultrasound to visualize hemodynamic changes after rodent spinal cord injury. J Neurosurg Spine. 2018;29(3): 306-313. https://doi.org/10.3171/2018.1.SPINE171202. 17. Deng X, Yang C, Gan J, et al. Long-term outcomes after small-bone-window posterior fossa decompression and duraplasty in adults with Chiari malformation type I. World neurosurgery. 2015;84(4): 998-1004. 18. Neale N, Ramayya A, Welch W. Surgical Management of Idiopathic Thoracic Spinal Cord Herniation. World Neurosurg. 2019;129: 81-84. https://doi.org/10.1016/j.wneu.2019.05.219. 19. Epstein FJ, Farmer JP, Schneider SJ. Intraoperative ultrasonography: an important surgical adjunct
for
intramedullary
tumors.
J
Neurosurg.
1991;74(5):
729-733.
16
https://doi.org/10.3171/jns.1991.74.5.0729. 20. Zhou H, Miller D, Schulte DM, et al. Intraoperative ultrasound assistance in treatment of intradural
spinal
tumours.
Clin
Neurol
Neurosurg.
2011;113(7):
531-537.
https://doi.org/10.1016/j.clineuro.2011.03.006. 21. Yang C, Li G, Fang J, et al. Intramedullary gangliogliomas: clinical features, surgical outcomes, and neuropathic scoliosis. Journal of neuro-oncology. 2014;116(1): 135-143. 22. Deng X, Wang K, Wu L, et al. Intraspinal hemangioblastomas: analysis of 92 cases in a single institution. Journal of Neurosurgery: Spine. 2014;21(2): 260-269. 23. Clark AJ, Wang DD, Lawton MT. Spinal cavernous malformations. Handbook of clinical neurology. Vol 143. Elsevier; 2017:303-308. 24. Regelsberger J, Fritzsche E, Langer N, Westphal M. Intraoperative sonography of intra- and extramedullary
tumors.
Ultrasound
Med
Biol.
2005;31(5):
593-598.
https://doi.org/10.1016/j.ultrasmedbio.2005.01.016. 25. Kane RA, Kruskal JB. Intraoperative ultrasonography of the brain and spine. Ultrasound Q. 2007;23(1): 23-39. http://doi.org/10.1097/01.ruq.0000263840.92560.72.
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FIGURE LEGENDS Figure 1. Clinical and radiological profiles of Case No. 1 (A) Spinal MRI in the local hospital revealed an intramedullary lesion (arrow) at the T6 level. (B) On this admission, spinal MRI showed the tumor (arrow) was not removed in the prior operation. (C&D) Intraoperative ultrasonography demonstrated a mixed-echoic lesion (arrows) in the axial plane. (E) CEUS showed the lesion was not enhanced. (F) In the longitudinal plane, the lesion (arrows) had a hypoechoic core. (G) With the assistance of intraoperative ultrasonography, the intramedullary lesion (arrow) was accurately localized and completely removed.
Figure 2. Radiological profiles of Case No. 2 (A) Preoperative spinal MRI revealed a small intramedullary lesion (arrow) at the T10 level. (B) Intraoperative ultrasonography showed a mixed-echoic lesion (arrows) with a hypoechoic core.
Figure 3. Clinical and radiological profiles of Case No. 3 (A&B) Preoperative spinal MRI showed an intramedullary tumor (arrow) at the C2-T2 levels. (C) After opening the dura mater, the boundaries of the tumor could not be identified. (D) Ultrasonography demonstrated a hyperechoic tumor (arrows). (E) CEUS delineated the tumor’s margins clearly (arrows). (F) Repeated ultrasound scans were performed during the tumor resection. (G) Eventually, the tumor was gross totally resected.
Table 1. Clinical profiles of the patients with intramedullary spinal lesions Case Gender Age Symptoms Duration Location No. (years) (months) of lesion 1 Male 39 Lower-extremity numbness 84 T6 and weakness 2 Female 45 Back pain, lower-extremity 12 T10 numbness 3 Male 42 Upper-extremity numbness 8 C2-T2 and weakness 4 Female 49 Back pain, upper-extremity 24 C4-C6 numbness 5 Female 28 Back pain, lower-extremity 6 C5-T2 numbness and weakness 6 Female 50 Back pain, lower-extremity 8 T12 weakness 7 Male 24 Back pain, lower-extremity 2 T7-T10 weakness 8 Female 29 Back pain, lower-extremity 2 T10-T11 numbness and weakness 9 Male 22 Back pain, right-extremity 2 T1-T2 numbness 10 Male 40 Lower-extremity numbness 6 C5-T2 11 Male 57 Back pain 60 T12-L3 12 Male 28 Upper-extremity numbness 2 C1-C5 and weakness 13 Male 64 Upper-extremity numbness 18 C6-C7 and weakness 14 Female 43 Neck pain, four-extremity 48 C1-C2 numbness Pre-op, pre-operative; Post-op, postoperative
Pathology Cavernous hemangioma Cavernous hemangioma Ependymoma
Follow-up (months) 16
McCormick Grading Pre-op Post-op Follow-up III III II
19
II
II
I
16
III
III
II
Astrocytoma
16
II
II
I
Ependymoma
16
IV
IV
IV
Astrocytoma
16
III
III
II
Astrocytoma
15
III
II
I
Cavernous hemangioma Cavernous hemangioma Ependymoma Ependymoma Anaplastic astrocytoma Astrocytoma
14
III
III
III
13
II
I
I
17 17 16
II I III
II I III
I I III
16
III
III
I
16
II
II
I
Ependymoma
HIGHLIGHTS： ：
Surgical resection of intramedullary tumors remains technically challenging.
Intraoperative ultrasound is of great value for localizing lesions.
Intraoperative ultrasound helps determining the extent of spinal surgery.
Intraoperative ultrasound reduces the invasiveness of spinal surgery.
ABBREVIATIONS LIST： ： CEUS: contrast-enhanced ultrasound CNS: central nervous system MRI: magnetic resonance imaging CSF: cerebrospinal fluid
CRediT author statement Bo Han: Conceptualization, Methodology, Writing-Original draft preparation. Dongfang Wu: Data collection and analysis, Software. Wenqing Jia: Visualization, Investigation. Song Lin: Data collection. Yulun Xu: Supervision, Writing-Reviewing and Editing,