Technique Assessment
Indocyanine Green Angiography in the Surgical Management of Cerebral Arteriovenous Malformations: Lessons Learned in 130 Consecutive Cases Hasan A. Zaidi, MD
BACKGROUND: Indocyanine green (ICG) angiography is commonly used to map the vascular configuration of cerebral arteriovenous malformations (AVMs) during resection. OBJECTIVE: To determine whether ICG improves rates of resection and clinical outcomes. METHODS: A retrospective chart review was done for all patients undergoing resection of an AVM by the senior author (R.F.S.) between 2007 and 2011. Operative reports, hospital records, and radiographic imaging were used to determine the use of ICG, the incidence of residual disease, and clinical outcomes. RESULTS: A total of 130 cases (56 ICG, 74 non-ICG) were identified. Average AVM grade (2.2 vs 2.4) and size (2.7 vs 2.7 cm) were similar between the ICG and non-ICG groups, respectively. ICG was more often used when the AVM nidus was close to the cortical surface (71.4% vs 17.6%; P = .001) or lobar (82.1% vs 54.1%; P = .008). Eighteen patients (13.8%) were noted to have residual disease. Reoperation rates and change in modified Rankin Scale score were not different between the 2 groups (12.5% vs 14.9%, P = .8; 0.6 vs 0.4, P = .17). There were no ICG-attributable complications. CONCLUSION: ICG videoangiography is a quick and safe method of intraoperatively mapping the angioarchitecture of superficial AVMs, but it is less helpful for deep-seated lesions. This modality alone does not improve the identification of residual disease or clinical outcomes. Surgeon experience with extensive study of preoperative vascular imaging is paramount to achieving acceptable clinical outcomes. Formal angiography remains the gold standard for the evaluation of AVM obliteration.
Adib A. Abla, MD Peter Nakaji, MD Shakeel A. Chowdhry, MD Felipe C. Albuquerque, MD Robert F. Spetzler, MD Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona Correspondence: Robert F. Spetzler, MD, c/o Neuroscience Publications, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, 350 W Thomas Rd, Phoenix, AZ 85013. E-mail: [email protected] Received, December 12, 2013. Accepted, January 24, 2014. Published Online, February 14, 2014. Copyright © 2014 by the Congress of Neurological Surgeons.
KEY WORDS: Angiography, Arteriovenous malformation, Gold standard, Indocyanine green, Resection Operative Neurosurgery 10:246–251, 2014
C
erebral arteriovenous malformations (AVMs) are surgically formidable lesions that require considerable skill to safely identify feeding vessels to disconnect, en passage vessels to avoid, and draining veins to preserve until the final stage of the procedure. Few realtime intraoperative imaging modalities are available to assist the surgeon in navigating the complex vascular anatomy of these lesions. Doppler duplex sonography may be difficult to interpret, particularly with higher-flow lesions, ABBREVIATIONS: AVM, arteriovenous malformation; DSA, digital subtraction angiography; ICG, indocyanine green
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DOI: 10.1227/NEU.0000000000000318
and disrupts the workflow during resection.1 Intraoperative cerebral angiography, although efficacious in identifying residual disease after the procedure,2-7 provides radiographic images that are not easily translatable to the open microsurgical anatomy. Fluorescence angiography, originally introduced in 1957 to evaluate retinal vascular pathology, was popularized in neurosurgery when it was coupled with nearinfrared video recording in 2003.8 Indocyanine green (ICG) videoangiography provides several distinct advantages: It is safe, quick, and inexpensive and requires no additional personnel or equipment other than the simple operating room microscope modifications. Images are acquired within minutes, immediately integrated into the
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ICG FOR AVM SURGERY
microscope with little interruption, and provide pictures more intuitive to interpret for the surgeon than conventional angiography or Doppler ultrasonography. Despite these obvious advantages and its increased popularity in the surgical treatment of AVMs, it is not clear at this point whether ICG videoangiography has actually led to an increased rate of complete resection and to improved identification and preservation of en passage vessels, resulting in improved clinical outcomes. In this article, we review our experience with 130 cerebral AVMs treated since the wide-scale application of this imaging modality.
METHODS We performed a retrospective review of all patients who underwent a craniotomy for microsurgical resection of an arteriovenous malformation at the Barrow Neurological Institute by the senior surgeon (R.F.S.) between 2007 and 2011. Because ICG-compatible microscopes were introduced in 2006 and used sparingly, we began our review after the first full year of implementation. Radiological imaging, operative reports,
in-hospital records, and clinic visits were analyzed. Basic demographic data and radiological findings, including Spetzler-Martin grade, proximity to the cortical surface, and anatomic location, were carefully recorded. Operative reports and formal angiograms were carefully reviewed to document the incidence of residual AVM, reopening for residual disease (if confirmatory angiography was performed intraoperatively before closure), return to operating room for resection of residual disease (if angiography was performed postoperatively), and use of ICG videoangiography at any point in the procedure (Figure 1). Clinic notes and patient correspondence were used to identify any long-term deficits and need for reoperation. Preoperative and postoperative modified Rankin scores and modified Rankin Scale score at last follow-up were compiled. The Fisher exact test was used to compare baseline characteristics between patient groups, and a value of P , .05 was considered statistically significant.
RESULTS Between 2007 and 2011, 130 patients underwent a craniotomy for microsurgical resection of a cerebral AVM. Other than 2007,
FIGURE 1. Intraoperative images during resection of a large right temporal arteriovenous malformation (AVM). A, sharp dissection around the nidus. B, early-phase indocyanine green (ICG) videoangiography showing several feeding vessels. C, latephase ICG videoangiography notable for 1 of 2 large varices draining the majority of the AVM. D, cauterization of the single large draining varix after circumferential dissection and cauterization of the AVM nidus. Used with permission from Barrow Neurological Institute.
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ZAIDI ET AL
TABLE 2. Distribution of Arteriovenous Malformation Size, Grade, Location, and Vascular Supplya Variable
All Patients ICG Used No ICG used
AVM grade (average) AVM Size (average), cm Presence of deep perforator supply, n (%) Infratentorial AVM, n (%) Lobar, n (%) AVM nidus at the cortical surface, n (%) a b
FIGURE 2. Frequency of the use of indocyanine green (ICG) vs traditional resection for cerebral arteriovenous malformations since 2007. Used with permission from Barrow Neurological Institute.
the second year after introduction, the frequency of the use of ICG videoangiography was well matched with traditional resection (Figure 2). Overall, 56 patients had ICG videoangiography performed at some point during the operation, whereas 74 patients did not (Table 1). There were slightly more male patients in our series (68 male vs 62 female patients), and there was a slightly higher average age among the ICG cohort (37.7 vs 34.2 years; Table 1). There was no statistically significant difference between the ICG and non-ICG groups in receiving preoperative Gamma Knife surgery (5.4% vs 2.7%) or embolization (60.7% vs 62.1%; Table 1). Preoperative Spetzler-Martin AVM score was similar between the ICG and non-ICG groups (2.2 vs 2.4), and average AVM diameter was identical (2.7 cm; Table 2). Although ICG was used less often among patients with deep arterial supply to the nidus, there was no statistically significant difference between the 2 groups (23.2% vs 28.4%; Table 2). ICG videoangiography was statistically more often used in AVMs that were lobar (82.1% vs 54.1%) and located near the
All Patients
ICG Used
No ICG used
Patients, n Female:male ratio Mean 6 SD age, y Preoperative embolization, n (%) Preoperative GKS
130 62:68 35.7 6 19.4 80 (61.5)
56 25:31 37.7 6 19.7 34 (60.7)
74 37:37 34.2 6 19.1 46 (62.1)
5 (3.8)
3 (5.4)
2 (2.7)
2.2 2.7 13 (23.2)
2.4 2.7 21 (28.4)
31 (23.8) 86 (66.2) 53 (40.8)
7 (12.5)b 46 (82.1)b 40 (71.4)b
24 (32.4)b 40 (54.1)b 13 (17.6)b
AVM, arteriovenous malformation. P , .05.
cortical surface (71.4% vs 17.6%); it was less often used when AVMs were located in the posterior fossa (12.5% vs 32.4%; Table 2). A confirmatory formal angiogram was performed either intraoperatively or postoperatively in all cases to ensure complete resection. Overall, there were 18 cases (13.9%) in which a formal angiogram (either intraoperatively or postoperatively) was notable for residual disease, necessitating another resection. The use of ICG videoangiography during resection did not statistically decrease the incidence of residual disease during the initial resection (12.5% vs 14.9%; P = .8; Table 3). Similarly, the preoperative, postoperative, and last follow-up modified Rankin Scale scores were not statistically different among the ICG and non-ICG groups, with all patients having similar clinical outcomes at each time interval (Table 3). There were no ICG-attributable complications.
DISCUSSION Our report here highlights the strengths and weaknesses of ICG videoangiography. It is a quick and safe method to map the
TABLE 3. Clinical Outcomes of Arteriovenous Malformation Surgery With Respect to Indocyanine Green Usea,b Variable
TABLE 1. Demographic Data, Preoperative Gamma Knife Surgery, and Embolization for Patients With Arteriovenous Malformation Resected With and Without Indocyanine Green Angiographya,b Variable
2.3 2.7 34 (26.2)
Confirmatory angiogram, n (%) Reoperation for residual AVM, n (%) Average 6 SD preoperative mRS score Average 6 SD change in mRS score at 6 wk Average 6 SD change in mRS score at last follow-up
All Patients
ICG Used
No ICG used
130 (100) 18 (13.9)
56 (100) 7 (12.5)
74 (100) 11 (14.9)
1.6 6 1.4
1.4 6 1.4
1.7 6 1.4
20.2 6 1.3 0.5 6 1.1
20.2 6 20.3 6 1.3 1.2 0.6 6 1.0 0.4 6 1.2
a a
GKS, Gamma Knife surgery; ICG, indocyanine green. b P , .05; no statistically significant differences were found between groups.
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AVM, arteriovenous malformation; ICG, indocyanine green; mRS, modified Rankin Scale. b P , .05; no statistically significant differences were found between groups.
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TABLE 4. Literature on Indocyanine Green Videoangiography for Arteriovenous Malformationsa Author, Year Takagi et al, 20079 Killory et al, 201010 Hanggi et al, 201013
1 10 15
Imaging Modality
Outcome Complete resection Complete resection Complete resection
ICG
ICG videoangiography is helpful in resecting residual cerebral AVM, especially in cases of diffuse-type AVM
ICG
Our experience suggests that it is less useful with deep-seated lesions or when AVM vessels are not on the surface; ICG angiography complements rather than replaces DSA This simple and safe real-time method is a useful additional tool that can potentially lower the surgical risk in complex AVMs and help avoid missed residuals
ICG
Ferroli et al, 201014
1
Complete resection
ICG
Jhawar et al, 201115 Faber et al, 201116
1
Complete resection Complete resection
ICG with Flow800 software ICG with Flow800 software
Kato et al, 201117
1
Complete resection
ICG with Flow800 software
Taddei et al, 201118 Takagi et al, 201219
9
Complete resection Complete resection
ICG
1
11
Authors’ Conclusions
ICG
Surgeons performing microvascular decompression should be aware that a diagnosis of vascular compression based on MRI without contrast administration could not exclude the presence of a pontine micro-AVM; ICG videoangiography provides an elegant means of showing the flow dynamics of these pathological vessels Flow-800 software analysis for ICG evaluation of AVMs may be a better option to analyze vascular anatomy Color-encoded aICG-VAG with FLOW-800 enables intraoperative real-time analysis of arterial and venous vessel architecture and therefore might increase the efficacy and safety of neurovascular surgery in a selected subset of superficial AVMs Flow-800 is a reliable and useful addition to microscope-integrated color ICG videoangiography; although its role is limited in deep-seated AVMs, if properly dissected and exposed, it can give useful information that can be easily interpretable and reproducible ICG videoangiography is easily performed during surgery for AVM and can confirm the completeness of the removal and may detect residual nidus, thus improving outcomes ICG videoangiography is helpful for resecting cerebral AVMs; it is especially effective in visualizing the nidus and superficial drainers, as well as changes in flow after clipping or coagulating of feeders
ICG-VAG, ICG videoangiography; AVM, arteriovenous malformation; DSA, digital subtraction angiography; ICG, indocyanine green; MRI, magnetic resonance imaging.
ICG FOR AVM SURGERY
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a
Patients, n
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ZAIDI ET AL
angioarchitecture of superficially located cerebral AVMs, adding just a few minutes per case with no identifiable adverse events in 130 consecutive patients. This is particularly helpful for novice surgeons or for teaching purposes in the operating room. ICG videoangiography is certainly an important tool in a neurosurgeon’s armamentarium, but one should be aware of its limitations. We show here that it does not result in improved clinical outcomes or reduce the incidence of residual disease. It is less useful for deep-seated lesions where there is poor light penetration and the entire nidus may not be visible through the viewfinder with panning of the microscope (ie, around corners in retrosigmoid approaches). It does not reliably detect residual disease, except in rare cases in which the draining vein and associated nidus are superficial and free from overlying blood or brain tissue.9,10 We therefore conclude that ICG videoangiography should be used only as an adjunctive tool in creating a plan of attack for superficially located AVMs; it should not be used as an isolated imaging modality to confirm residual disease or to identify en passage vessels. Extensive study of preoperative digital subtraction angiography (DSA) and surgeon experience are the most important factors determining clinical outcomes and the probability of a successful resection in the first stage. A formal angiogram remains the gold standard for the detection of residual disease and should be performed on all patients undergoing resection. A considerable amount of controversy remains on how to effectively use ICG videoangiography during AVM resection. Unlike for aneurysms, for which there is a plethora of data indicating equivalence to DSA in identifying residual disease,11,12 just 9 reports have been published on the subject since 2007 (Table 4). These are limited only to small case series with anecdotal data. In 2010, our group published a 10-patient prospective series collecting surgeon feedback after ICG videoangiography during resection of cerebral AVMs. In 9 of 10 patients (all of whom had superficially located AVMs), the primary surgeon concluded that ICG videoangiography was helpful in guiding the resection.10 In 1 case, ICG helped to change the course of the procedure by highlighting areas of suspicious vasculature. In other cases such as a deep-seated third ventricular AVM approached via an interhemispheric craniotomy, the ICG run was not helpful because only limited portions of the lesion were visible in the microscope viewfinder at any one time. Our experience with ICG has grown since this preliminary report, and we have found that it is most helpful in identifying the major draining veins and how quickly they fill. It also helps delineate the nidus on the surface and highlights the arterial inputs. If ICG shows an early vessel, it may be useful to guide further resection and to decrease the number of intraoperative and postoperative angiograms needed. However, if it does not, the presence of residual has not been excluded. Other authors have published conflicting results. Taddei et al18 reviewed their preliminary experience in the treatment of 9 AVMs and concluded that ICG alone can confirm the completeness of removal and detect residual disease, even suggesting that this
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modality can replace intraoperative/postoperative DSA. Similarly, Hanggi et al13 reviewed their series of 15 AVMs and noted that ICG was “very useful” in the detection of residual nidus at the end of the procedure and that en passage vessels were clearly identifiable in all cases. Finally, Takagi et al9 reported a case of a 2-year-old girl with a diffuse-type AVM with residual disease not visible on initial postoperative angiogram but picked up by ICG videoangiography on repeat surgery. From this case, the authors concluded that ICG is able to effectively detect the presence of residual disease. Our report is subject to all the limitations and biases inherent in a retrospective review. Although the ICG and non-ICG groups were similar in terms of grade and size, one can argue that in a retrospective fashion they may not be strictly comparable.
CONCLUSION To the best of our knowledge, this is the largest such reported series in the literature and highlights the advantages of and drawbacks to this imaging modality. It is safe, quick, and reliable in identifying the architecture of superficially located AVMs. At our institution, we use ICG primarily for lesions in which the nidus is located superficially and have stopped using it altogether for deepseated lesions. Nevertheless, caution should be exercised in relying solely on this imaging modality for any AVM surgery. It is advisable that surgeons study the preoperative DSA to understand the vascular configuration and use ICG only as a supplement to confirm their impressions. Intraoperative/postoperative DSA is still the standard of care to confirm the completeness of resection. Future improvements in fluorescence angiography, including color-coded ICG, may improve reliability and deserve further study. Disclosure The authors have no personal financial or institutional interest in any of the drugs, materials, or devices described in this article.
REFERENCES 1. Goodkin R, McKhann GM, Haynor DR, Mayberg MR, Eskridge JM, Winn HR. Persistent feeding arteries to angiographically completely embolized arteriovenous malformation demonstrated by intraoperative color-flow Doppler testing: report of two cases. Surg Neurol. 1995;44:326-332. 2. Anegawa S, Hayashi T, Torigoe R, Harada K, Kihara S. Intraoperative angiography in the resection of arteriovenous malformations. J Neurosurg. 1994;80(1):73-78. 3. Barrow DL, Boyer KL, Joseph GJ. Intraoperative angiography in the management of neurovascular disorders. Neurosurgery. 1992;30(2):153-159. 4. Bartal AD, Tirosh MS, Weinstein M. Angiographic control during total excision of a cerebral arteriovenous malformation: technical note. J Neurosurg. 1968;29(2): 211-213. 5. Bauer BL. Intraoperative angiography in cerebral aneurysm and AV-malformation. Neurosurg Rev. 1984;7(2-3):209-217. 6. Derdeyn CP, Moran CJ, Cross DT, Grubb RL Jr, Dacey RG Jr. Intraoperative digital subtraction angiography: a review of 112 consecutive examinations. AJNR Am J Neuroradiol. 1995;16(2):307-318. 7. Ghosh S, Levy ML, Stanley P, Nelson M, Giannotta SL, McComb JG. Intraoperative angiography in the management of pediatric vascular disorders. Pediatr Neurosurg. 1999;30(1):16-22.
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ICG FOR AVM SURGERY
8. Raabe A, Beck J, Gerlach R, Zimmermann M, Seifert V. Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow. Neurosurgery. 2003;52(1):132-139. 9. Takagi Y, Kikuta K, Nozaki K, Sawamura K, Hashimoto N. Detection of a residual nidus by surgical microscope-integrated intraoperative near-infrared indocyanine green videoangiography in a child with a cerebral arteriovenous malformation. J Neurosurg. 2007;107(5 suppl):416-418. 10. Killory BD, Nakaji P, Gonzales LF, Ponce FA, Wait SD, Spetzler RF. Prospective evaluation of surgical microscope-integrated intraoperative near-infrared indocyanine green angiography during cerebral arteriovenous malformation surgery. Neurosurgery. 2009;65(3):456-462. 11. Raabe A, Nakaji P, Beck J, et al. Prospective evaluation of surgical microscopeintegrated intraoperative near-infrared indocyanine green videoangiography during aneurysm surgery. J Neurosurg. 2005;103(6):982-989. 12. Dashti R, Laakso A, Niemela M, Porras M, Hernesniemi J. Microscope-integrated near-infrared indocyanine green videoangiography during surgery of intracranial aneurysms: the Helsinki experience. Surg Neurol. 2009;71(5):543-550. 13. Hanggi D, Etminan N, Steiger HJ. The impact of microscope-integrated intraoperative near-infrared indocyanine green videoangiography on surgery of arteriovenous malformations and dural arteriovenous fistulae. Neurosurgery. 2010; 67(4):1094-1103. 14. Ferroli P, Acerbi F, Broggi M, Broggi G. Arteriovenous micromalformation of the trigeminal root: intraoperative diagnosis with indocyanine green videoangiography: case report. Neurosurgery. 2010;67(3 suppl operative): onsE309-onsE310. 15. Jhawar SS, Kato Y, Oda J, Oguri D, Sano H, Hirose Y. FLOW 800-assisted surgery for arteriovenous malformation. J Clin Neurosci. 2011;18(11):1556-1557. 16. Faber F, Thon N, Fesl G, et al. Enhanced analysis of intracerebral arteriovenous malformations by the intraoperative use of analytical indocyanine green videoangiography: technical note. Acta Neurochir (Wien). 2011;153(11):2181-2187. 17. Kato Y, Jhawar SS, Oda J, et al. Preliminary evaluation of the role of surgical microscope-integrated intraoperative FLOW 800 colored indocyanine fluorescence angiography in arteriovenous malformation surgery. Neurol India. 2011;59 (6):829-832. 18. Taddei G, Tommasi CD, Ricci A, Galzio RJ. Arteriovenous malformations and intraoperative indocyanine green videoangiography: preliminary experience. Neurol India. 2011;59(1):97-100. 19. Takagi Y, Sawamura K, Hashimoto N, Miyamoto S. Evaluation of serial intraoperative surgical microscope-integrated intraoperative near-infrared indocyanine green videoangiography in patients with cerebral arteriovenous malformations. Neurosurgery. 2012;70[ONS Suppl 1]:ons34-ons43.
COMMENTS
T
he use of indocyanine green (ICG) videoangiography has been well documented for cerebral aneurysm surgery and certainly has value that supplements the role of digital subtraction angiography. The value of ICG for arteriovenous malformation (AVM) surgery has not been similarly demonstrated and at best remains suspect. In this study, the authors present a review of their recent experience with AVM surgery. In some cases, ICG was used, and in others, this type of angiography was not attempted. The experience is anecdotal and lacking scientific rigor but
OPERATIVE NEUROSURGERY
nonetheless provides interesting insight into the lack of benefit of ICG videoangiography for AVM surgery. Use of this technique did not improve any measure of surgical outcome, and identification of residual AVM was absolutely dependent on intraoperative or postoperative digital subtraction angiography. This information mirrors my own experience with ICG, and I have abandoned this technique for AVM surgery. Robert A. Solomon New York, New York
T
he authors present an interesting discussion regarding the lack of utility of indocyanine green (ICG) angiography in the resection of arteriovenous malformations (AVMs). The authors reviewed their institutional experience of 130 surgical resections of AVMs, of which 56 had ICG angiography performed during the resection and 74 did not. The use of ICG angiography did not result in a statistically significant decrease in the presence of residual AVM on formal intraoperative or postoperative angiography (12.5% vs 14.9%; P = .8). The use of ICG angiography was not systematically applied, so making firm conclusions on the basis of these data is difficult. However, we agree with the authors’ assertion that ICG angiography is not a reliable alternative to formal angiography in AVM surgery. The utility of ICG angiography is entirely dependent on the visual clarity of the operative field. If the cortex lies between the observer and the vessels of interest, then it will provide little value. This is precisely why it can be quite helpful in aneurysm surgery (when the parent vessels, aneurysm neck, and aneurysm dome are often directly in view) and why it is of limited value in AVM surgery. To quote the late astronomer Carl Sagan, “absence of evidence is not evidence of absence.” The authors astutely mention this while discussing the limited value of ICG angiography in deep, narrow surgical fields such as in the posterior fossa. The most common cause of failed complete AVM resection is simply not exposing the entire nidus. This is why ICG angiography fails in AVM surgery and the reason we do not use ICG angiography for AVM resections. Nothing can currently substitute meticulous study and knowledge of the preoperative angiographic anatomy of the AVM before and during surgical excision, as well as postoperative formal angiography. The authors should also be commended for their publication of “negative” results. In the current competitive atmosphere of manuscript publications, it is often felt that only positive results are worthy of description. However, negative findings can be just as valuable in tailoring our current treatment paradigms. We hope that this article serves as a strong example of this lesson to future researchers. Matthew R. Fusco Christopher S. Ogilvy Boston, Massachusetts
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Indocyanine Green Angiography in the Surgical Management of Cerebral Arteriovenous Malformations: Lessons Learned in 130 Consecutive Cases Hasan A. Zaidi, MD
BACKGROUND: Indocyanine green (ICG) angiography is commonly used to map the vascular configuration of cerebral arteriovenous malformations (AVMs) during resection. OBJECTIVE: To determine whether ICG improves rates of resection and clinical outcomes. METHODS: A retrospective chart review was done for all patients undergoing resection of an AVM by the senior author (R.F.S.) between 2007 and 2011. Operative reports, hospital records, and radiographic imaging were used to determine the use of ICG, the incidence of residual disease, and clinical outcomes. RESULTS: A total of 130 cases (56 ICG, 74 non-ICG) were identified. Average AVM grade (2.2 vs 2.4) and size (2.7 vs 2.7 cm) were similar between the ICG and non-ICG groups, respectively. ICG was more often used when the AVM nidus was close to the cortical surface (71.4% vs 17.6%; P = .001) or lobar (82.1% vs 54.1%; P = .008). Eighteen patients (13.8%) were noted to have residual disease. Reoperation rates and change in modified Rankin Scale score were not different between the 2 groups (12.5% vs 14.9%, P = .8; 0.6 vs 0.4, P = .17). There were no ICG-attributable complications. CONCLUSION: ICG videoangiography is a quick and safe method of intraoperatively mapping the angioarchitecture of superficial AVMs, but it is less helpful for deep-seated lesions. This modality alone does not improve the identification of residual disease or clinical outcomes. Surgeon experience with extensive study of preoperative vascular imaging is paramount to achieving acceptable clinical outcomes. Formal angiography remains the gold standard for the evaluation of AVM obliteration.
Adib A. Abla, MD Peter Nakaji, MD Shakeel A. Chowdhry, MD Felipe C. Albuquerque, MD Robert F. Spetzler, MD Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona Correspondence: Robert F. Spetzler, MD, c/o Neuroscience Publications, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, 350 W Thomas Rd, Phoenix, AZ 85013. E-mail: [email protected] Received, December 12, 2013. Accepted, January 24, 2014. Published Online, February 14, 2014. Copyright © 2014 by the Congress of Neurological Surgeons.
KEY WORDS: Angiography, Arteriovenous malformation, Gold standard, Indocyanine green, Resection Operative Neurosurgery 10:246–251, 2014
C
erebral arteriovenous malformations (AVMs) are surgically formidable lesions that require considerable skill to safely identify feeding vessels to disconnect, en passage vessels to avoid, and draining veins to preserve until the final stage of the procedure. Few realtime intraoperative imaging modalities are available to assist the surgeon in navigating the complex vascular anatomy of these lesions. Doppler duplex sonography may be difficult to interpret, particularly with higher-flow lesions, ABBREVIATIONS: AVM, arteriovenous malformation; DSA, digital subtraction angiography; ICG, indocyanine green
246 | VOLUME 10 | NUMBER 2 | JUNE 2014
DOI: 10.1227/NEU.0000000000000318
and disrupts the workflow during resection.1 Intraoperative cerebral angiography, although efficacious in identifying residual disease after the procedure,2-7 provides radiographic images that are not easily translatable to the open microsurgical anatomy. Fluorescence angiography, originally introduced in 1957 to evaluate retinal vascular pathology, was popularized in neurosurgery when it was coupled with nearinfrared video recording in 2003.8 Indocyanine green (ICG) videoangiography provides several distinct advantages: It is safe, quick, and inexpensive and requires no additional personnel or equipment other than the simple operating room microscope modifications. Images are acquired within minutes, immediately integrated into the
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ICG FOR AVM SURGERY
microscope with little interruption, and provide pictures more intuitive to interpret for the surgeon than conventional angiography or Doppler ultrasonography. Despite these obvious advantages and its increased popularity in the surgical treatment of AVMs, it is not clear at this point whether ICG videoangiography has actually led to an increased rate of complete resection and to improved identification and preservation of en passage vessels, resulting in improved clinical outcomes. In this article, we review our experience with 130 cerebral AVMs treated since the wide-scale application of this imaging modality.
METHODS We performed a retrospective review of all patients who underwent a craniotomy for microsurgical resection of an arteriovenous malformation at the Barrow Neurological Institute by the senior surgeon (R.F.S.) between 2007 and 2011. Because ICG-compatible microscopes were introduced in 2006 and used sparingly, we began our review after the first full year of implementation. Radiological imaging, operative reports,
in-hospital records, and clinic visits were analyzed. Basic demographic data and radiological findings, including Spetzler-Martin grade, proximity to the cortical surface, and anatomic location, were carefully recorded. Operative reports and formal angiograms were carefully reviewed to document the incidence of residual AVM, reopening for residual disease (if confirmatory angiography was performed intraoperatively before closure), return to operating room for resection of residual disease (if angiography was performed postoperatively), and use of ICG videoangiography at any point in the procedure (Figure 1). Clinic notes and patient correspondence were used to identify any long-term deficits and need for reoperation. Preoperative and postoperative modified Rankin scores and modified Rankin Scale score at last follow-up were compiled. The Fisher exact test was used to compare baseline characteristics between patient groups, and a value of P , .05 was considered statistically significant.
RESULTS Between 2007 and 2011, 130 patients underwent a craniotomy for microsurgical resection of a cerebral AVM. Other than 2007,
FIGURE 1. Intraoperative images during resection of a large right temporal arteriovenous malformation (AVM). A, sharp dissection around the nidus. B, early-phase indocyanine green (ICG) videoangiography showing several feeding vessels. C, latephase ICG videoangiography notable for 1 of 2 large varices draining the majority of the AVM. D, cauterization of the single large draining varix after circumferential dissection and cauterization of the AVM nidus. Used with permission from Barrow Neurological Institute.
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ZAIDI ET AL
TABLE 2. Distribution of Arteriovenous Malformation Size, Grade, Location, and Vascular Supplya Variable
All Patients ICG Used No ICG used
AVM grade (average) AVM Size (average), cm Presence of deep perforator supply, n (%) Infratentorial AVM, n (%) Lobar, n (%) AVM nidus at the cortical surface, n (%) a b
FIGURE 2. Frequency of the use of indocyanine green (ICG) vs traditional resection for cerebral arteriovenous malformations since 2007. Used with permission from Barrow Neurological Institute.
the second year after introduction, the frequency of the use of ICG videoangiography was well matched with traditional resection (Figure 2). Overall, 56 patients had ICG videoangiography performed at some point during the operation, whereas 74 patients did not (Table 1). There were slightly more male patients in our series (68 male vs 62 female patients), and there was a slightly higher average age among the ICG cohort (37.7 vs 34.2 years; Table 1). There was no statistically significant difference between the ICG and non-ICG groups in receiving preoperative Gamma Knife surgery (5.4% vs 2.7%) or embolization (60.7% vs 62.1%; Table 1). Preoperative Spetzler-Martin AVM score was similar between the ICG and non-ICG groups (2.2 vs 2.4), and average AVM diameter was identical (2.7 cm; Table 2). Although ICG was used less often among patients with deep arterial supply to the nidus, there was no statistically significant difference between the 2 groups (23.2% vs 28.4%; Table 2). ICG videoangiography was statistically more often used in AVMs that were lobar (82.1% vs 54.1%) and located near the
All Patients
ICG Used
No ICG used
Patients, n Female:male ratio Mean 6 SD age, y Preoperative embolization, n (%) Preoperative GKS
130 62:68 35.7 6 19.4 80 (61.5)
56 25:31 37.7 6 19.7 34 (60.7)
74 37:37 34.2 6 19.1 46 (62.1)
5 (3.8)
3 (5.4)
2 (2.7)
2.2 2.7 13 (23.2)
2.4 2.7 21 (28.4)
31 (23.8) 86 (66.2) 53 (40.8)
7 (12.5)b 46 (82.1)b 40 (71.4)b
24 (32.4)b 40 (54.1)b 13 (17.6)b
AVM, arteriovenous malformation. P , .05.
cortical surface (71.4% vs 17.6%); it was less often used when AVMs were located in the posterior fossa (12.5% vs 32.4%; Table 2). A confirmatory formal angiogram was performed either intraoperatively or postoperatively in all cases to ensure complete resection. Overall, there were 18 cases (13.9%) in which a formal angiogram (either intraoperatively or postoperatively) was notable for residual disease, necessitating another resection. The use of ICG videoangiography during resection did not statistically decrease the incidence of residual disease during the initial resection (12.5% vs 14.9%; P = .8; Table 3). Similarly, the preoperative, postoperative, and last follow-up modified Rankin Scale scores were not statistically different among the ICG and non-ICG groups, with all patients having similar clinical outcomes at each time interval (Table 3). There were no ICG-attributable complications.
DISCUSSION Our report here highlights the strengths and weaknesses of ICG videoangiography. It is a quick and safe method to map the
TABLE 3. Clinical Outcomes of Arteriovenous Malformation Surgery With Respect to Indocyanine Green Usea,b Variable
TABLE 1. Demographic Data, Preoperative Gamma Knife Surgery, and Embolization for Patients With Arteriovenous Malformation Resected With and Without Indocyanine Green Angiographya,b Variable
2.3 2.7 34 (26.2)
Confirmatory angiogram, n (%) Reoperation for residual AVM, n (%) Average 6 SD preoperative mRS score Average 6 SD change in mRS score at 6 wk Average 6 SD change in mRS score at last follow-up
All Patients
ICG Used
No ICG used
130 (100) 18 (13.9)
56 (100) 7 (12.5)
74 (100) 11 (14.9)
1.6 6 1.4
1.4 6 1.4
1.7 6 1.4
20.2 6 1.3 0.5 6 1.1
20.2 6 20.3 6 1.3 1.2 0.6 6 1.0 0.4 6 1.2
a a
GKS, Gamma Knife surgery; ICG, indocyanine green. b P , .05; no statistically significant differences were found between groups.
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AVM, arteriovenous malformation; ICG, indocyanine green; mRS, modified Rankin Scale. b P , .05; no statistically significant differences were found between groups.
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TABLE 4. Literature on Indocyanine Green Videoangiography for Arteriovenous Malformationsa Author, Year Takagi et al, 20079 Killory et al, 201010 Hanggi et al, 201013
1 10 15
Imaging Modality
Outcome Complete resection Complete resection Complete resection
ICG
ICG videoangiography is helpful in resecting residual cerebral AVM, especially in cases of diffuse-type AVM
ICG
Our experience suggests that it is less useful with deep-seated lesions or when AVM vessels are not on the surface; ICG angiography complements rather than replaces DSA This simple and safe real-time method is a useful additional tool that can potentially lower the surgical risk in complex AVMs and help avoid missed residuals
ICG
Ferroli et al, 201014
1
Complete resection
ICG
Jhawar et al, 201115 Faber et al, 201116
1
Complete resection Complete resection
ICG with Flow800 software ICG with Flow800 software
Kato et al, 201117
1
Complete resection
ICG with Flow800 software
Taddei et al, 201118 Takagi et al, 201219
9
Complete resection Complete resection
ICG
1
11
Authors’ Conclusions
ICG
Surgeons performing microvascular decompression should be aware that a diagnosis of vascular compression based on MRI without contrast administration could not exclude the presence of a pontine micro-AVM; ICG videoangiography provides an elegant means of showing the flow dynamics of these pathological vessels Flow-800 software analysis for ICG evaluation of AVMs may be a better option to analyze vascular anatomy Color-encoded aICG-VAG with FLOW-800 enables intraoperative real-time analysis of arterial and venous vessel architecture and therefore might increase the efficacy and safety of neurovascular surgery in a selected subset of superficial AVMs Flow-800 is a reliable and useful addition to microscope-integrated color ICG videoangiography; although its role is limited in deep-seated AVMs, if properly dissected and exposed, it can give useful information that can be easily interpretable and reproducible ICG videoangiography is easily performed during surgery for AVM and can confirm the completeness of the removal and may detect residual nidus, thus improving outcomes ICG videoangiography is helpful for resecting cerebral AVMs; it is especially effective in visualizing the nidus and superficial drainers, as well as changes in flow after clipping or coagulating of feeders
ICG-VAG, ICG videoangiography; AVM, arteriovenous malformation; DSA, digital subtraction angiography; ICG, indocyanine green; MRI, magnetic resonance imaging.
ICG FOR AVM SURGERY
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a
Patients, n
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ZAIDI ET AL
angioarchitecture of superficially located cerebral AVMs, adding just a few minutes per case with no identifiable adverse events in 130 consecutive patients. This is particularly helpful for novice surgeons or for teaching purposes in the operating room. ICG videoangiography is certainly an important tool in a neurosurgeon’s armamentarium, but one should be aware of its limitations. We show here that it does not result in improved clinical outcomes or reduce the incidence of residual disease. It is less useful for deep-seated lesions where there is poor light penetration and the entire nidus may not be visible through the viewfinder with panning of the microscope (ie, around corners in retrosigmoid approaches). It does not reliably detect residual disease, except in rare cases in which the draining vein and associated nidus are superficial and free from overlying blood or brain tissue.9,10 We therefore conclude that ICG videoangiography should be used only as an adjunctive tool in creating a plan of attack for superficially located AVMs; it should not be used as an isolated imaging modality to confirm residual disease or to identify en passage vessels. Extensive study of preoperative digital subtraction angiography (DSA) and surgeon experience are the most important factors determining clinical outcomes and the probability of a successful resection in the first stage. A formal angiogram remains the gold standard for the detection of residual disease and should be performed on all patients undergoing resection. A considerable amount of controversy remains on how to effectively use ICG videoangiography during AVM resection. Unlike for aneurysms, for which there is a plethora of data indicating equivalence to DSA in identifying residual disease,11,12 just 9 reports have been published on the subject since 2007 (Table 4). These are limited only to small case series with anecdotal data. In 2010, our group published a 10-patient prospective series collecting surgeon feedback after ICG videoangiography during resection of cerebral AVMs. In 9 of 10 patients (all of whom had superficially located AVMs), the primary surgeon concluded that ICG videoangiography was helpful in guiding the resection.10 In 1 case, ICG helped to change the course of the procedure by highlighting areas of suspicious vasculature. In other cases such as a deep-seated third ventricular AVM approached via an interhemispheric craniotomy, the ICG run was not helpful because only limited portions of the lesion were visible in the microscope viewfinder at any one time. Our experience with ICG has grown since this preliminary report, and we have found that it is most helpful in identifying the major draining veins and how quickly they fill. It also helps delineate the nidus on the surface and highlights the arterial inputs. If ICG shows an early vessel, it may be useful to guide further resection and to decrease the number of intraoperative and postoperative angiograms needed. However, if it does not, the presence of residual has not been excluded. Other authors have published conflicting results. Taddei et al18 reviewed their preliminary experience in the treatment of 9 AVMs and concluded that ICG alone can confirm the completeness of removal and detect residual disease, even suggesting that this
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modality can replace intraoperative/postoperative DSA. Similarly, Hanggi et al13 reviewed their series of 15 AVMs and noted that ICG was “very useful” in the detection of residual nidus at the end of the procedure and that en passage vessels were clearly identifiable in all cases. Finally, Takagi et al9 reported a case of a 2-year-old girl with a diffuse-type AVM with residual disease not visible on initial postoperative angiogram but picked up by ICG videoangiography on repeat surgery. From this case, the authors concluded that ICG is able to effectively detect the presence of residual disease. Our report is subject to all the limitations and biases inherent in a retrospective review. Although the ICG and non-ICG groups were similar in terms of grade and size, one can argue that in a retrospective fashion they may not be strictly comparable.
CONCLUSION To the best of our knowledge, this is the largest such reported series in the literature and highlights the advantages of and drawbacks to this imaging modality. It is safe, quick, and reliable in identifying the architecture of superficially located AVMs. At our institution, we use ICG primarily for lesions in which the nidus is located superficially and have stopped using it altogether for deepseated lesions. Nevertheless, caution should be exercised in relying solely on this imaging modality for any AVM surgery. It is advisable that surgeons study the preoperative DSA to understand the vascular configuration and use ICG only as a supplement to confirm their impressions. Intraoperative/postoperative DSA is still the standard of care to confirm the completeness of resection. Future improvements in fluorescence angiography, including color-coded ICG, may improve reliability and deserve further study. Disclosure The authors have no personal financial or institutional interest in any of the drugs, materials, or devices described in this article.
REFERENCES 1. Goodkin R, McKhann GM, Haynor DR, Mayberg MR, Eskridge JM, Winn HR. Persistent feeding arteries to angiographically completely embolized arteriovenous malformation demonstrated by intraoperative color-flow Doppler testing: report of two cases. Surg Neurol. 1995;44:326-332. 2. Anegawa S, Hayashi T, Torigoe R, Harada K, Kihara S. Intraoperative angiography in the resection of arteriovenous malformations. J Neurosurg. 1994;80(1):73-78. 3. Barrow DL, Boyer KL, Joseph GJ. Intraoperative angiography in the management of neurovascular disorders. Neurosurgery. 1992;30(2):153-159. 4. Bartal AD, Tirosh MS, Weinstein M. Angiographic control during total excision of a cerebral arteriovenous malformation: technical note. J Neurosurg. 1968;29(2): 211-213. 5. Bauer BL. Intraoperative angiography in cerebral aneurysm and AV-malformation. Neurosurg Rev. 1984;7(2-3):209-217. 6. Derdeyn CP, Moran CJ, Cross DT, Grubb RL Jr, Dacey RG Jr. Intraoperative digital subtraction angiography: a review of 112 consecutive examinations. AJNR Am J Neuroradiol. 1995;16(2):307-318. 7. Ghosh S, Levy ML, Stanley P, Nelson M, Giannotta SL, McComb JG. Intraoperative angiography in the management of pediatric vascular disorders. Pediatr Neurosurg. 1999;30(1):16-22.
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ICG FOR AVM SURGERY
8. Raabe A, Beck J, Gerlach R, Zimmermann M, Seifert V. Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow. Neurosurgery. 2003;52(1):132-139. 9. Takagi Y, Kikuta K, Nozaki K, Sawamura K, Hashimoto N. Detection of a residual nidus by surgical microscope-integrated intraoperative near-infrared indocyanine green videoangiography in a child with a cerebral arteriovenous malformation. J Neurosurg. 2007;107(5 suppl):416-418. 10. Killory BD, Nakaji P, Gonzales LF, Ponce FA, Wait SD, Spetzler RF. Prospective evaluation of surgical microscope-integrated intraoperative near-infrared indocyanine green angiography during cerebral arteriovenous malformation surgery. Neurosurgery. 2009;65(3):456-462. 11. Raabe A, Nakaji P, Beck J, et al. Prospective evaluation of surgical microscopeintegrated intraoperative near-infrared indocyanine green videoangiography during aneurysm surgery. J Neurosurg. 2005;103(6):982-989. 12. Dashti R, Laakso A, Niemela M, Porras M, Hernesniemi J. Microscope-integrated near-infrared indocyanine green videoangiography during surgery of intracranial aneurysms: the Helsinki experience. Surg Neurol. 2009;71(5):543-550. 13. Hanggi D, Etminan N, Steiger HJ. The impact of microscope-integrated intraoperative near-infrared indocyanine green videoangiography on surgery of arteriovenous malformations and dural arteriovenous fistulae. Neurosurgery. 2010; 67(4):1094-1103. 14. Ferroli P, Acerbi F, Broggi M, Broggi G. Arteriovenous micromalformation of the trigeminal root: intraoperative diagnosis with indocyanine green videoangiography: case report. Neurosurgery. 2010;67(3 suppl operative): onsE309-onsE310. 15. Jhawar SS, Kato Y, Oda J, Oguri D, Sano H, Hirose Y. FLOW 800-assisted surgery for arteriovenous malformation. J Clin Neurosci. 2011;18(11):1556-1557. 16. Faber F, Thon N, Fesl G, et al. Enhanced analysis of intracerebral arteriovenous malformations by the intraoperative use of analytical indocyanine green videoangiography: technical note. Acta Neurochir (Wien). 2011;153(11):2181-2187. 17. Kato Y, Jhawar SS, Oda J, et al. Preliminary evaluation of the role of surgical microscope-integrated intraoperative FLOW 800 colored indocyanine fluorescence angiography in arteriovenous malformation surgery. Neurol India. 2011;59 (6):829-832. 18. Taddei G, Tommasi CD, Ricci A, Galzio RJ. Arteriovenous malformations and intraoperative indocyanine green videoangiography: preliminary experience. Neurol India. 2011;59(1):97-100. 19. Takagi Y, Sawamura K, Hashimoto N, Miyamoto S. Evaluation of serial intraoperative surgical microscope-integrated intraoperative near-infrared indocyanine green videoangiography in patients with cerebral arteriovenous malformations. Neurosurgery. 2012;70[ONS Suppl 1]:ons34-ons43.
COMMENTS
T
he use of indocyanine green (ICG) videoangiography has been well documented for cerebral aneurysm surgery and certainly has value that supplements the role of digital subtraction angiography. The value of ICG for arteriovenous malformation (AVM) surgery has not been similarly demonstrated and at best remains suspect. In this study, the authors present a review of their recent experience with AVM surgery. In some cases, ICG was used, and in others, this type of angiography was not attempted. The experience is anecdotal and lacking scientific rigor but
OPERATIVE NEUROSURGERY
nonetheless provides interesting insight into the lack of benefit of ICG videoangiography for AVM surgery. Use of this technique did not improve any measure of surgical outcome, and identification of residual AVM was absolutely dependent on intraoperative or postoperative digital subtraction angiography. This information mirrors my own experience with ICG, and I have abandoned this technique for AVM surgery. Robert A. Solomon New York, New York
T
he authors present an interesting discussion regarding the lack of utility of indocyanine green (ICG) angiography in the resection of arteriovenous malformations (AVMs). The authors reviewed their institutional experience of 130 surgical resections of AVMs, of which 56 had ICG angiography performed during the resection and 74 did not. The use of ICG angiography did not result in a statistically significant decrease in the presence of residual AVM on formal intraoperative or postoperative angiography (12.5% vs 14.9%; P = .8). The use of ICG angiography was not systematically applied, so making firm conclusions on the basis of these data is difficult. However, we agree with the authors’ assertion that ICG angiography is not a reliable alternative to formal angiography in AVM surgery. The utility of ICG angiography is entirely dependent on the visual clarity of the operative field. If the cortex lies between the observer and the vessels of interest, then it will provide little value. This is precisely why it can be quite helpful in aneurysm surgery (when the parent vessels, aneurysm neck, and aneurysm dome are often directly in view) and why it is of limited value in AVM surgery. To quote the late astronomer Carl Sagan, “absence of evidence is not evidence of absence.” The authors astutely mention this while discussing the limited value of ICG angiography in deep, narrow surgical fields such as in the posterior fossa. The most common cause of failed complete AVM resection is simply not exposing the entire nidus. This is why ICG angiography fails in AVM surgery and the reason we do not use ICG angiography for AVM resections. Nothing can currently substitute meticulous study and knowledge of the preoperative angiographic anatomy of the AVM before and during surgical excision, as well as postoperative formal angiography. The authors should also be commended for their publication of “negative” results. In the current competitive atmosphere of manuscript publications, it is often felt that only positive results are worthy of description. However, negative findings can be just as valuable in tailoring our current treatment paradigms. We hope that this article serves as a strong example of this lesson to future researchers. Matthew R. Fusco Christopher S. Ogilvy Boston, Massachusetts
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