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Efficacy of FLOW 800 with Indocyanine Green Videoangiography for the Quantitative Assessment of Flow Dynamics in Cerebral Arteriovenous Malformation Surgery Kenji Fukuda, Hiroharu Kataoka, Norio Nakajima, Jun Masuoka, Tetsu Satow, Koji Iihara
Key words Arteriovenous malformation - FLOW 800 - Indocyanine green videoangiography - Quantitative assessment -
Abbreviations and Acronyms AI: Arbitrary intensity AVM: Arteriovenous malformation DSA: Digital subtraction angiography ICG: Indocyanine green MVTT: Microhemodynamics microvascular transit time T1/2 FI: Time to the half-maximum fluorescence intensity Department of Neurosurgery, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan To whom correspondence should be addressed: Koji Iihara, M.D., Ph.D. [E-mail: [email protected]] Citation: World Neurosurg. (2015) 83, 2:203-210. http://dx.doi.org/10.1016/j.wneu.2014.07.012 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2015 Elsevier Inc. All rights reserved.
INTRODUCTION The application of indocyanine green (ICG) videoangiography in cerebrovascular neurosurgery is practiced widely. Conventional ICG videoangiography is a real-time intraoperative imaging tool that helps identify the vascular architecture, flow direction, and qualitative blood flow transit speed. These features enable surgeons to intraoperatively distinguish between arteries and veins or between normal and abnormal vascular components such as a cerebral aneurysm, arteriovenous malformation (AVM), and dural arteriovenous fistula (11, 13, 18, 23, 25). Conventional ICG videoangiography also helps identify vessel patency during aneurysm clipping, intracranial-extracranial bypass, and carotid endarterectomy (8, 19, 23, 30); however, one drawback of this conventional technique is that a precise quantitative analysis of blood flow dynamics cannot be achieved. This analysis of blood flow is especially important during AVM surgery
- OBJECTIVE:
To evaluate the quantitative assessment of flow dynamics during surgery for arteriovenous malformations (AVMs) with FLOW 800 with indocyanine green videoangiography.
- METHODS:
Changes in flow dynamics in the superficial AVM components (feeder, nidus, and drainer), the adjacent cortical artery, and the cortical vein surrounding AVM were evaluated. Analysis was performed at predissection, postclipping of the feeders, and postresection of the nidus with the use of quantitative values of the maximum fluorescence intensity, time to half-maximum fluorescence intensity (T1/2 FI), and the fluorescence intensity rate at T1/2 FI semiautomatically obtained with the use of FLOW 800 software.
- RESULTS:
FLOW 800 assessments were performed in 7 cases. The time difference between the T1/2 FI, defined as transit time, in the cortical artery and the drainer was prolonged from 0.08 0.65 seconds to 2.63 1.79 seconds (P < 0.0001) at postfeeder clipping phase. The transit time between the cortical artery and the cortical vein was reduced to 3.76 1.37 seconds at post feeder clipping phase (P [ 0.024) and 2.63 0.80 seconds at final phase (P [ 0.005) compared with 4.56 1.47 seconds at predissection phase. The maximum intensity and the fluorescence intensity rate at T1/2 FI were not significantly different at these phases, excluding the maximum intensity of the drainer decreasing from 533 271 to 399 217 (P [ 0.006) at post feeder clipping phase.
- CONCLUSION:
FLOW 800 analysis with indocyanine green videoangiography provides the real-time hemodynamic status of the AVMs and adjacent brain at various stages of resection. This technique is feasible to resect AVMs more safely and convincingly.
because a precise understanding of the vascular architecture and changes in flow dynamics help surgeons perform surgery in a safe and efficient fashion. FLOW 800 software was developed as an additional analytical imaging tool to analyze blood flow dynamics with the use of ICG videoangiography. This technique enables an objective and quantitative analysis presented visually as a color map and ICG intensity-time curve. Previous studies reported the quantitative flow analysis in cerebrovascular surgery (14, 15, 17, 20, 24, 29); however, changes in flow dynamics via the use of time and fluorescence based parameters during AVM resection are not yet available in detail. In this study, the authors aimed to evaluate whether FLOW 800 analysis with repeated ICG videoangiography at various stages of
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resection for AVMs is useful for evaluating the hemodynamic changes in AVMs and adjacent brain. To analyze time and fluorescence based parameters, we used quantitative values semiautomatically obtained by applied FLOW 800 software. PATIENTS AND METHODS This study population included 7 patients (3 male, mean age: 33.3 years, range: 9e64 years) who underwent resection of cerebral AVMs between January 2010 and March 2012. Three patients presented with seizures and intracerebral hemorrhages. AVM was incidentally diagnosed in 1 patient. Spetzler-Martin grade I AVM was identified in 2 patients, grade II in 4 patients, and grade III in 1 patient (Table 1).
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Table 1. Patients Characteristics Case
Age (y)/ Sex
AVM Location
S&M Grade
Presentation
Location of Nidus
Maximum Size of Nidus, mm
ICG Injection, Times
Intra- or Postoperative DSA
1
27/F
Lt. parietal
2
Hemorrhage
Superficial
28
5
Yes
2
29/F
Lt. temporal
2
Seizure
Superficial
19
5
Yes
3
34/F
Rt. insula
1
Hemorrhage
Deep
10
5
Yes
4
9/F
Lt. parietal
3
Seizure
Deep
22
5
Yes
5
36/M
Lt. temporal
2
Seizure
Deep
20
6
Yes
6
34/M
Rt. frontal
2
Incidental
Superficial
42
4
Yes
7
64/M
Rt. cerebellum
1
Hemorrhage
Superficial
8
3
Yes
Deep means that nidus is covered by parenchyma and superficial means that nidus faces on the surface of the parenchyma. AVM, arteriovenous malformation; S&M, Spetzler and Martin; ICG, indocyanine green; DSA, digital subtraction angiography; F, female; M, male.
Three patients with deep feeders, which were considered difficult to detect in the superficial operative field, underwent preoperative embolization using N-butyl2-cyanoacrylate. To detect residual AVMs, intraoperative digital subtraction angiography (DSA) was performed in 2 cases and postoperative DSA in 5 cases. ICG Videoangiography After intravenous bolus injection of ICG, the operative field was illuminated by the use of a microscope-integrated light source with a wavelength covering the ICG absorption band (range, 700e850 nm; maximum, 805 nm). Arterial, capillary, and venous flow images were observed on the video screen in real time. The recommended dose of ICG for this type of videoangiography is 0.2e0.5 mg/kg. In this study, all patients received an ICG injection at a dose of 0.1 mg/kg as a bolus. This dose is sufficient for analysis and enables us to perform repeated ICG videoangiography at least 5e10 minutes after the last injection. All images were recorded using the microscopic hardware and could be confirmed easily, immediately, and repeatedly. All operations were performed using OPMI Pentero (Carl Zeiss Co., Oberkochen, Germany). TIMING OF ICG VIDEOANGIOGRAPHY Intraoperative ICG videoangiography was first performed immediately after the dura was opened to analyze baseline flow dynamics of the normal vascular architecture and superficial AVM components. ICG videoangiography was sequentially
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performed to evaluate the flow reduction of the nidus and drainer after the main feeders were occluded by stepwise clipping of the feeders. Finally, ICG videoangiography was performed after total resection of the nidus. FLOW 800 Functions For additionally evaluating blood flow dynamics, a FLOW 800 function was installed in the Pentero microscope. Temporal fluorescence projection uses colors, defined as a color map that allows us to instantly identify the direction and sequence of blood flow. The target vessel is shown as a continuous color scale, depending on the time it takes to reach the ICG dye. Red represents the initial blood inflow, followed by a gradient color scale in blue for the subsequent blood flow sequence. Another map uses different shades of gray based on the maximum fluorescence intensity, which was used for the quantitative analysis of vascular flow dynamics with an ICG intensity-time curve. Management of the Quantitative Analysis of Vascular Flow Dynamics by FLOW 800 Quantitative analysis of vascular flow dynamics was performed as follows: In 1 session, maximum 8 regions of interest (ROIs) were set on a superficial target vessel on the maximum intensity map. Fluorescence intensities were measured in arbitrary intensity units (AIs). Each ICG intensity-time curve and the complementary quantitative values of the time to the half-maximum fluorescence intensity (T1/2 FI [seconds(s)]) from the start of the ICG
analysis, maximum intensity (AI), and fluorescence rate at T1/2 FI (AI/s) were semiautomatically obtained in the same screen, T1/2 FI as “Delay” and fluorescence rate at T1/2 FI as “Slope”. The T1/2 FI by itself has no meaning because the timing taken to start the ICG analysis was not consistent; however, to assess transit time, defined as the time difference between the T1/2 FI in 2 points in the same phase, we evaluated the blood flow dynamics changes in each vascular component. The ROIs were set on the superficial AVM components (main feeders, nidus, and main drainers), cortical artery, and cortical vein adjacent to the AVM. On preoperative DSA, we confirmed that the adjacent cortical artery and the vein surrounding the AVM in the operative field were not associated directly with the AVM. The ROIs of the main feeders and drainers were evaluated at 2 points in some patients when the area of perfusion was apparently different. The ROIs of the cortical artery and vein were evaluated at 1 point in each patient. The total number of evaluated ROIs for the main feeders was 10 (2 points for each case 1, 4, and 5; 1 point for each case 2, 3, 6, and 7), for the nidus was 4 points (1 point for each case 1, 3, 6, and 7), and for the main drainer was 11 points (2 points for each case 1, 2, 5, and 6; 1 point for each case 3, 4, and 7). In 3 patients with a deep-seated nidus, the ROIs could not be set on the nidus because it was covered with parenchyma. The ROIs in each situation were set on the same point. FLOW 800 analysis was performed at the time of dural opening (baseline phase), after maximum flow
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Table 2. The Quantitative Analysis of Maximum Intensity and Fluorescence Intensity Rate at Time to Half-Maximum Fluorescence Intensity (T1/2 FI) in the Timing of Baseline, Postfeeder Clipping, and Final Phase Maximum Intensity (AI)
Fluorescence Intensity Rate at T1/2 FI (AI/s)
Baseline Phase
Postfeeder Clipping Phase
Final Phase
Baseline Phase
Postfeeder Clipping Phase
Final Phase
387.6 252.5
473.7 360.8
420.7 230.6
88.9 103.0
125.1 131.2
90.1 54.4
Cortical vein (n ¼ 7)
260.7 94.5
318.9 147.5
315.7 139.0
40.2 28.6
45.0 23.7
52.6 35.4
Arterial feeder (n ¼ 10)
490.5 249.5
Cortical artery (n ¼ 7)
113.1 88.1
Nidus (n ¼ 4)
520.5 274.5
437.5 283.6
136.5 116.0
114.6 121.3
Draining vein (n ¼ 11)
533.4 271.6
399.8 217.3*
138.1 104.3
271.8 621.4
AI, Arbitrary intensity. *Significantly lower (P ¼ 0.006) compared with baseline phase on draining vein.
reduction of the nidus by stepwise clipping of the feeders (postfeeder clipping phase), and after resection of the nidus (final phase). Quantitative Assessment of FLOW 800 Analysis We evaluated whether FLOW 800 could be used for the quantitative assessment of flow dynamic changes induced by the maximum intensity and fluorescence intensity rate at T1/2 FI in each AVM component (feeder, nidus, and drainer) and cortical artery and vein adjacent to the AVM at baseline, postfeeder clipping, and the final phase. In addition, the transit times between the cortical artery, defined as an index artery, and the AVM components (nidus and drainers), at baseline and postfeeder clipping, were evaluated to confirm the effectiveness of a maximum flow reduction of the nidus by stepwise feeder clipping. Moreover, we compared transit time between the cortical artery and the cortical vein to indicate changes in the cortical perfusion surrounding the AVM during the 3 phases. Statistical Analysis A paired t test was used to compare the quantitative values at paired sites among the baseline, postfeeder clipping, and final phases as appropriate. P < 0.05 was considered statistically significant. RESULTS A total of 33 ICG videoangiographies were successfully performed. The average
number of ICG injections per operation was 4.75 (range, 3e6) (Table 1). FLOW 800 analyses were completely achieved in a few minutes in all patients. Quantitative assessments were achieved in all patients. The calculated maximum intensity and fluorescence intensity rate at T1/2 FI are summarized in Table 2. The calculated transit time from the cortical artery to the nidus, draining vein, and cortical vein during the 3 phases are summarized in Tables 3 and 4. The maximum intensity and fluorescence intensity rate at T1/2 were not significantly different during the 3 phases; however, the maximum intensity of the drainer at the post feeder clipping phase decreased from 533 271 to 399 217 (P ¼ 0.006). After a maximum flow reduction of the nidus by stepwise feeder clipping, transit time between the cortical artery and the drainer was prolonged from 0.08 0.65 seconds to 2.63 1.79 seconds (P < 0.0001). After resection of the nidus, disappearance of the AV shunt to the superficial drainer was
confirmed. Transit time between the cortical artery and the cortical vein reduced from 4.56 1.47 seconds at predissection of the nidus to 3.76 1.37 seconds at postclipping of the feeders (P ¼ 0.024) and 2.63 0.80 seconds at postresection of the nidus (P ¼ 0.005). Total resection of the nidus was confirmed using postoperative DSA in 5 cases and intraoperative DSA in 2 cases. In 1 case, a deep-seated tiny residual nidus with a deep drainer was detected on postoperative angiography just after the operation and was re-resected on the same day. None of the patients experienced an adverse reaction to the ICG dye. No new symptoms or aggravation of neuroradiologic examinations caused by normal perfusion pressure breakthrough occurred. No new permanent deficits caused by the operation occurred. ILLUSTRATIVE CASE A 29-year-old woman who was 25 weeks’ pregnant was admitted because of motor
Table 3. The Comparison of Transit Times Using Half-Maximum Fluorescence Intensity (T1/2 FI) Between Cortical Artery and Nidus and Drainer in the Timing of Baseline and Postfeeder Clipping Phase Baseline Phase, Seconds
Postfeeder Clipping Phase, Seconds
Transit time between cortical artery and nidus (n ¼ 4)
0.30 0.48
1.32 1.52
Transit time between cortical artery and drainer (n ¼ 11)
0.08 0.65
2.63 1.79
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P Value 0.125 < 0.0001
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Table 4. The Comparison of Transit Times Using Half-Maximum Fluorescence Intensity (T1/2 FI) Between Cortical Artery and Cortical Vein in the Timing of Baseline, Postfeeder Clipping, and Final Phase Case
Baseline Phase, seconds
Postfeeder Clipping Phase, seconds
Final Phase, seconds
1
4.36
2.78
1.77
2
3.58
2.53
1.58
3
4.88
4.32
3.16
4
5.97
4.2
2.66
5
2.48
2.64
2.36
6
3.49
3.17
2.74
7
7.13
6.7
4.15
4.56 1.47
3.76 1.37*
2.63 0.80y
Mean
*Significantly faster (P ¼ 0.024) compared with baseline phase. ySignificantly faster (P ¼ 0.005) compared with baseline phase.
transit time between the cortical artery and the cortical vein reduced to 4.36 seconds at predissection, 2.78 seconds at postfeeder clipping, and 1.77 seconds at postresection of the nidus (Figure 2DeI). This reduction possibly indicates an improvement in impaired perfusion in the adjacent tissue surrounding the AVM in the presence of arteriovenous shunts. The maximum intensity and fluorescence intensity rate at T1/2 in each phase were not consistent. Total resection of AVMs was confirmed using ICG videoangiography and postoperative DSA. The patient’s pregnancy was successfully managed, and she vaginally delivered a healthy infant 10 weeks after AVM resection.
DISCUSSION aphasia, right hemiparesis, and right sensory disturbance. Computed tomography revealed intracerebral hematoma in the left parietal lobe (Figure 1A). DSA revealed a left parietal AVM of Spetzler and Martin grade II (Figure 1B). The operation was performed 4 weeks after admission. General anesthesia was conducted with fetal heart rate monitoring. Intraoperative DSA was not performed. After craniotomy and opening of the dura mater (Figure 1C), an initial ICG videoangiography was performed. FLOW 800 analysis was performed, and the ICG intensity-time curve was obtained by setting at 7 ROIs (1 cortical artery defined as the
index artery, 1 cortical vein, 2 main feeders, 1 nidus, and 2 main drainers) on the screen (Figure 2A, D, and G). Similarly, FLOW 800 analysis was performed at postfeeder clipping and postresection of the AVM. After 2 main feeders were clipped, the reduced flow in the nidus and drainer was confirmed by observing the color change (Figure 2B), and transit times between the cortical artery and the nidus, and the 2 main drainers increased to þ1.42, þ1.93, and þ4.39 seconds, respectively (Figure 2E and H). After resection of the nidus, disappearance of the arteriovenous shunt to the superficial drainer was confirmed (Figure 2C), and
Figure 1. Case 1. (A) Computed tomography scan revealed a left parietal intraparenchymal hematoma. (B) Digital subtraction angiography revealed a
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Quantitative Assessment of FLOW 800 Analysis FLOW 800 is an additional analytical imaging tool that can be used to analyze blood flow dynamics. Color maps can help instantly identify the direction and sequence of blood flow by showing a continuous color scale that depends on the time taken by the ICG dye to reach the area. This system is especially intuitive and beneficial for immediately distinguishing between arterial and venous flow, as well as feeders and drainers, because these images are static and in color, compared with those obtained with conventional ICG videoangiography
left parietal arteriovenous malformation of Spetzler and Martin grade II. (C) Intraoperative view using a left parietal approach before dissection.
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Figure 2. Case 1. The analysis of vascular flow during surgery for an arteriovenous malformation (AVM) using FLOW 800. (A) The color map at prefeeder clipping. The AVM components were identified instinctively. (B) The color map at postfeeder clipping. The nidus and drainer became darker, indicating a decrease in the shunt flow. (C) The color map during post-AVM resection. The disappearance of the arteriovenous shunt to the nidus and drainer were confirmed. The regions of interest (ROIs) to analyze flow dynamics using FLOW 800 and the transit times between cortical artery defined as index artery and each component as below. (D) The ROIs at prefeeder clipping. 1, cortical artery; 2, feeder 1a; 3, feeder 1b; 4, nidus; 5, drainer 1a; 6, drainer 1b; 7, cortical vein. (E) The ROIs at postfeeder
(6, 9, 28). In addition to this function, it is possible to analyze the vascular flow dynamics quantitatively with an ICG intensity-time curve. Several studies have demonstrated the usefulness of FLOW 800 to assess the hemodynamic status with quantitative time and fluorescence-based
clipping. 1, cortical artery; 2, nidus; 3, drainer 1a; 4, drainer 1b; 5, cortical vein. (F) The ROIs at post AVM resection. 1, cortical artery; 2, cortical vein. The diagram of blood flow and quantitative values in each ROI (GeI). (G) The numbers 1e7 correspond to the numbers in (D). The color of each number corresponds to the quantitative values of the time to the half-maximum fluorescence intensity (T1/2 FI) on the right side. (H) The numbers 1e5 corresponds to the numbers in (E). The color of each number corresponds to the quantitative values of the T1/2 FI on the right side. (I) The numbers 1 and 2 corresponds to the numbers in (F). The color of each number corresponds to the quantitative values of T1/2 FI on the right side.
parameters in cerebrovascular surgery (14, 15, 17, 20, 24, 29). This quantitative analysis could be helpful especially for the understanding of flow dynamics change at various stages in cerebrovascular surgery (14, 15, 17, 29); however, detailed quantitative analysis has not been established at
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the various stage of resection in AVM surgery. In addition, several parameters using time and fluorescence intensity of FLOW 800 analysis as maximum intensity, time to peak (the time interval between the initial appearance of fluorescence and the maximum fluorescence intensity),
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time to half half-maximal fluorescence, rise time (the interval between 10% and 90% of the maximum fluorescence), blood flow index (the ratio of maximum fluorescence intensity to rise time), and microvascular transit time exist in these studies, and these parameters have not been established. In this study, we used time- and fluorescence-based parameters of T1/2 FI, maximum intensity, and fluorescence rate at T1/2 FI semiautomatically obtained easily and immediately on the screen of the microscope by the applied FLOW 800 software. This is important because this method provides the realtime hemodynamic status of the AVMs and adjacent brain at various stages of resection without complicated calculation. This is first to demonstrate the efficacy of FLOW 800 for the understanding of hemodynamic changes at various stages of resection in AVM surgery. Our quantitative assessments of transit times using T1/2 FI between the cortical artery and each AVM component revealed a decrease in the AV shunt flow after maximum feeder clipping. Flow reduction can be assessed and reassessed at the stage of stepwise feeder clipping when residual main feeder is suspicious by referring to the preoperative assessment. Several ICG injections were made, and maximum flow reduction could be done at this study. These flow pattern changes were only detected by conventional ICG videoangiography to determine the extent of a gradual decrease of ICG dye that passed each AVM component. These quantitative assessments by FLOW 800 provide precise information about a flow reduction of the nidus and drainer. Hashimoto et al. (12) mentioned to the effect of maximum flow reduction of the nidus by stepwise feeder clipping to control intranidal pressure and to avoid uncontrollable bleeding from the nidus and adjacent brain at the early stage of cerebral AVM surgery. Conventional ICG videoangiography can also help identify the flow direction and reduction of AVM instantly; however, this objective information can guide next surgical steps to resect AVMs more safely, effectively, and convincingly, and minimize the sequelae of unanticipated complications. In this study, we also demonstrated the usefulness of FLOW 800 for the assessment of cortical perfusion during AVM surgery. Some authors have reported
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successful analyses in cortical perfusion using ICG videoangiography during decompressive craniectomy for malignant stroke, revascularization for moyamoya disease, surgical obliteration for dural arteriovenous fistula, and subarachnoid hemorrhage (7, 14, 15, 29, 31). In particular, Czabanka et al. (7) reported that the cortical microhemodynamics microvascular transit time (MVTT) increased in patients with moyamoya disease patients compared with that in patients with atherosclerotic cerebrovascular disease and control patients. The MVTT was defined as the time taken for maximum fluorescence intensity from the cortical artery to the cortical vein. The authors specified that the MVTT indirectly represented microvascular blood flow velocity. The transit time Czabanka et al. (7) calculated was similar to the transit time using T1/2 FI in this study; therefore, it is true that the T1/2 FI indirectly represents microvascular blood flow velocity. The problem of their method is that specific software was required to analyze the MVTT; however, it is easy to calculate the T1/2 FI at 2 points in AVMs and surrounding AVM components using FLOW 800 because the T1/2 FI at one point is automatically obtained. Several reports in human and animal models have proven that the local cerebral blood flow surrounding an AVM improves after resection of the AVM by xenon-enhanced computed tomography scan, directional Doppler technique, positron emission tomography, or magnetic resonance perfusion imaging (4, 10, 16, 21, 22, 26, 27). The mechanism underlying low cortical perfusion in the adjacent brain tissues surrounding an AVM involves disturbed cerebral blood flow and vascular reactivity due to the low resistance of the nidus and high flow transnidal shunts (1-3, 27). Furthermore, the impaired cortical perfusion surrounding an AVM improves after resection of AVM. In 1 sulcal AVM case, Kamp et al. (17) suggested that the differences between the arterial and parenchymal fluorescence peaks were longer before than that after occlusion of the AVM, indicating impaired perfusion in the adjacent tissue by arteriovenous shunts. Our results that transit time using T1/2 FI between the cortical artery and vein surrounding the
AVM were shortened after resecting AVMs support this finding. Although the ICG videoangiography for the assessment of cortical perfusion is not fully established, FLOW 800 analysis with transit time may assess the improvement of the impaired cortical perfusion. Study Strengths and Limitations Ng et al. (20) have already described the use of quantitative flow analysis by FLOW 800 during AVM surgery. They showed the mean T1/2 FI and fluorescence intensity rate at T1/2 FI for the arterial feeder, draining vein, and normal cortex in 8 patients; however, these were quantitatively evaluated only at the predissection phase. In our study, we described the dynamic changes in blood flow in each AVM component during surgery and changes in cortical perfusion surrounding the AVM before and after the resection of AVMs using an ICG time intensity curve and revealed that the T1/2 FI parameter was useful for assessing the reduction of AV shunt in the drainers by maximum flow reduction of the nidus and improvement of cortical perfusion in the adjacent brain after resection of AVM. Our study is the first to identify the real-time hemodynamic status of the AVMs and adjacent brain. In this study, we also examined the maximum intensity and fluorescence intensity rate at T1/2 FI, and these parameters did not demonstrate any significant changes during AVM surgery, except for the maximum intensity of the drainer before and after feeder clipping. Several factors, including the dose and timing of the ICG injection, blood pressure, cardiac output, and microscope settings, might influence the results of ICG analysis (17). Because these factors cannot be strictly managed, they might influence the results of the ICG analysis. Kamp et al. (17) indicated that the fluorescence-based parameter such as the maximum intensity and fluorescence intensity rate at T1/2 FI showed large variations, and that they were hard to define, although to minimize variability, the microscope setting, bolus size, injection speed, and ICG injection timing were kept almost the same. On the other hand, they concluded that a timeassociated parameter, such as transit times between 2 points, was subject to less variability to exhibit the perfusion of the cerebral vessels and the cortex. Thus,
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taking our results into consideration, evaluating the time-associated parameter would be more helpful during AVM surgery. The limitation of FLOW 800 analysis is that this technique is only available for superficial AVMs. During surgery, the reduced shunt flow of a deep-seated nidus could be confirmed by a gradual decrease in the superficial drainer’s flow through the nidus when covered with parenchyma; however, when a deep-seated nidus or drainer exists, it is difficult to prove the total resection of AVM by ICG videoangiography (11, 18, 28). Indeed, a deepseated tiny residual nidus with a deep drainer was detected on postoperative angiography and re-resected on the same day in one case in this study. Therefore, we think that intraoperative or postoperative DSA is necessary when deepseated nidus or drainer exists, although there are several limitations as complications, radiation exposure, and additional time in DSA (5, 28). Another study limitation is that the sample size of 7 cases is small, and future studies with more cases are required to provide the assessment of flow dynamics in AVM surgery.
CONCLUSIONS Quantitative assessment of flow dynamics with FLOW 800 using ICG intensity-time curves enabled us to identify the real-time hemodynamic status of the AVMs and adjacent brain easily and immediately during AVM surgery. Time-associated parameter of transit time using using T1/2 FI is useful especially for this assessment. This novel technique facilitates the maximum flow reduction by stepwise feeder clipping and resection of AVMs more safely and convincingly. Intraoperative or postoperative DSA is necessary for the confirmation of total resection of AVMs with deep-seated lesions. REFERENCES 1. Awad IA, Magdinec M, Schubert A: Intracranial hypertension after resection of cerebral arteriovenous malformations. Predisposing factors and management strategy. Stroke 25:611-620, 1994. 2. Batjer HH, Devous MD Sr, Meyer YJ, Purdy PD, Samson DS: Cerebrovascular hemodynamics in arteriovenous malformation complicated by normal perfusion pressure breakthrough. Neurosurgery 22:503-509, 1988.
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7. Czabanka M, Pena-Tapia P, Schubert GA, Woitzik J, Vajkoczy P, Schmiedek P: Characterization of cortical microvascularization in adult moyamoya disease. Stroke 39:1703-1709, 2008.
19. Kim DL, Cohen-Gadol AA: Indocyanine-green videoangiogram to assess collateral circulation before arterial sacrifice for management of complex vascular and neoplastic lesions: technical note. World Neurosurg 79:404.e1-404.e6, 2013.
8. de Oliveira JG, Beck J, Seifert V, Teixeira MJ, Raabe A: Assessment of flow in perforating arteries during intracranial aneurysm surgery using intraoperative near-infrared indocyanine green videoangiography. Neurosurgery 62:1300-1310, 2008.
20. Ng YP, King NK, Wan KR, Wang E, Ng I: Uses and limitations of indocyanine green videoangiography for flow analysis in arteriovenous malformation surgery. J Clin Neurosci 20:224-232, 2013.
9. Faber F, Thon N, Fesl G, Rachinger W, Guckler R, Tonn JC, Schichor C: Enhanced analysis of intracerebral arterioveneous malformations by the intraoperative use of analytical indocyanine green videoangiography: technical note. Acta Neurochir (Wien) 153:2181-2187, 2011. 10. Guo WY, Wu YT, Wu HM, Chung WY, Kao YH, Yeh TC, Shiau CY, Pan DH, Chang YC, Hsieh JC: Toward normal perfusion after radiosurgery: perfusion MR imaging with independent component analysis of brain arteriovenous malformations. AJNR Am J Neuroradiol 25:1636-1644, 2004. 11. Hanggi D, Etminan N, Steiger HJ: The impact of microscope-integrated intraoperative nearinfrared indocyanine green videoangiography on surgery of arteriovenous malformations and dural arteriovenous fistulae. Neurosurgery 67:1094-1103; discussion 1103-1094, 2010. 12. Hashimoto N, Nozaki K, Takagi Y, Kikuta K, Mikuni N: Surgery of cerebral arteriovenous malformations. Neurosurgery 61:375-387; discussion 387-389, 2007. 13. Hettige S, Walsh D: Indocyanine green videoangiography as an aid to surgical treatment of spinal dural arteriovenous fistulae. Acta Neurochir (Wien) 152:533-536, 2010. 14. Holling M, Brokinkel B, Ewelt C, Fischer BR, Stummer W: Dynamic ICG fluorescence provides better intraoperative understanding of arteriovenous fistulae. Neurosurgery 73:ons93-ons98; discussion ons99, 2013.
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21. Nornes H, Grip A: Hemodynamic aspects of cerebral arteriovenous malformations. J Neurosurg 53:456-464, 1980. 22. Okabe T, Meyer JS, Okayasu H, Harper R, Rose J, Grossman RG, Centeno R, Tachibana H, Lee YY: Xenon-enhanced CT CBF measurements in cerebral AVM’s before and after excision. Contribution to pathogenesis and treatment. J Neurosurg 59: 21-31, 1983. 23. Raabe A, Nakaji P, Beck J, Kim LJ, Hsu FP, Kamerman JD, Seifert V, Spetzler RF: Prospective evaluation of surgical microscope-integrated intraoperative near-infrared indocyanine green videoangiography during aneurysm surgery. J Neurosurg 103:982-989, 2005. 24. Schubert GA, Seiz-Rosenhagen M, Ortler M, Czabanka M, Scheufler KM, Thome C: Cortical indocyanine green videography for quantification of acute hypoperfusion after subarachnoid hemorrhage: a feasibility study. Neurosurgery 71: ons260-ons267; discussion ons267-ons268, 2012. 25. Schuette AJ, Cawley CM, Barrow DL: Indocyanine green videoangiography in the management of dural arteriovenous fistulae. Neurosurgery 67: 658-662; discussion 662, 2010. 26. Scott BB, McGillicuddy JE, Seeger JF, Kindt GW, Giannotta SL: Vascular dynamics of an experimental cerebral arteriovenous shunt in the primate. Surg Neurol 10:34-38, 1978. 27. Spetzler RF, Wilson CB, Weinstein P, Mehdorn M, Townsend J, Telles D: Normal perfusion pressure
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breakthrough theory. Clin Neurosurg 25:651-672, 1978.
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30. Woitzik J, Horn P, Vajkoczy P, Schmiedek P: Intraoperative control of extracranial-intracranial bypass patency by near-infrared indocyanine green videoangiography. J Neurosurg 102:692-698, 2005.
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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. Received 6 January 2014; accepted 15 July 2014; published online 18 July 2014 Citation: World Neurosurg. (2015) 83, 2:203-210. http://dx.doi.org/10.1016/j.wneu.2014.07.012 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2015 Elsevier Inc. All rights reserved.
WORLD FEDERATION OF NEUROSURGICAL SOCIETIES Mission Statement To facilitate the personal association of neurological surgeons throughout the world. To aid in the exchange and dissemination of knowledge and ideas in the field of neurological surgery. To encourage research in neurological surgery and allied sciences. To address issues of neurosurgical demography. To address issues of Public Health. To implement, improve and promote the standards of neurosurgical care and training worldwide.
Membership Services (www.wfns.org) Teresa Chen Hsiao-Hui (Teresa) Chen Office Manager, WFNS Central Office World Federation of Neurosurgical Societies 5 Rue du Marché 1260 Nyon, Vaud, Switzerland Tel: +41 (0) 22 3624303 Fax: +41 (0) 22 3624352 Email: [email protected]
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Efficacy of FLOW 800 with Indocyanine Green Videoangiography for the Quantitative Assessment of Flow Dynamics in Cerebral Arteriovenous Malformation Surgery Kenji Fukuda, Hiroharu Kataoka, Norio Nakajima, Jun Masuoka, Tetsu Satow, Koji Iihara
Key words Arteriovenous malformation - FLOW 800 - Indocyanine green videoangiography - Quantitative assessment -
Abbreviations and Acronyms AI: Arbitrary intensity AVM: Arteriovenous malformation DSA: Digital subtraction angiography ICG: Indocyanine green MVTT: Microhemodynamics microvascular transit time T1/2 FI: Time to the half-maximum fluorescence intensity Department of Neurosurgery, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan To whom correspondence should be addressed: Koji Iihara, M.D., Ph.D. [E-mail: [email protected]] Citation: World Neurosurg. (2015) 83, 2:203-210. http://dx.doi.org/10.1016/j.wneu.2014.07.012 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2015 Elsevier Inc. All rights reserved.
INTRODUCTION The application of indocyanine green (ICG) videoangiography in cerebrovascular neurosurgery is practiced widely. Conventional ICG videoangiography is a real-time intraoperative imaging tool that helps identify the vascular architecture, flow direction, and qualitative blood flow transit speed. These features enable surgeons to intraoperatively distinguish between arteries and veins or between normal and abnormal vascular components such as a cerebral aneurysm, arteriovenous malformation (AVM), and dural arteriovenous fistula (11, 13, 18, 23, 25). Conventional ICG videoangiography also helps identify vessel patency during aneurysm clipping, intracranial-extracranial bypass, and carotid endarterectomy (8, 19, 23, 30); however, one drawback of this conventional technique is that a precise quantitative analysis of blood flow dynamics cannot be achieved. This analysis of blood flow is especially important during AVM surgery
- OBJECTIVE:
To evaluate the quantitative assessment of flow dynamics during surgery for arteriovenous malformations (AVMs) with FLOW 800 with indocyanine green videoangiography.
- METHODS:
Changes in flow dynamics in the superficial AVM components (feeder, nidus, and drainer), the adjacent cortical artery, and the cortical vein surrounding AVM were evaluated. Analysis was performed at predissection, postclipping of the feeders, and postresection of the nidus with the use of quantitative values of the maximum fluorescence intensity, time to half-maximum fluorescence intensity (T1/2 FI), and the fluorescence intensity rate at T1/2 FI semiautomatically obtained with the use of FLOW 800 software.
- RESULTS:
FLOW 800 assessments were performed in 7 cases. The time difference between the T1/2 FI, defined as transit time, in the cortical artery and the drainer was prolonged from 0.08 0.65 seconds to 2.63 1.79 seconds (P < 0.0001) at postfeeder clipping phase. The transit time between the cortical artery and the cortical vein was reduced to 3.76 1.37 seconds at post feeder clipping phase (P [ 0.024) and 2.63 0.80 seconds at final phase (P [ 0.005) compared with 4.56 1.47 seconds at predissection phase. The maximum intensity and the fluorescence intensity rate at T1/2 FI were not significantly different at these phases, excluding the maximum intensity of the drainer decreasing from 533 271 to 399 217 (P [ 0.006) at post feeder clipping phase.
- CONCLUSION:
FLOW 800 analysis with indocyanine green videoangiography provides the real-time hemodynamic status of the AVMs and adjacent brain at various stages of resection. This technique is feasible to resect AVMs more safely and convincingly.
because a precise understanding of the vascular architecture and changes in flow dynamics help surgeons perform surgery in a safe and efficient fashion. FLOW 800 software was developed as an additional analytical imaging tool to analyze blood flow dynamics with the use of ICG videoangiography. This technique enables an objective and quantitative analysis presented visually as a color map and ICG intensity-time curve. Previous studies reported the quantitative flow analysis in cerebrovascular surgery (14, 15, 17, 20, 24, 29); however, changes in flow dynamics via the use of time and fluorescence based parameters during AVM resection are not yet available in detail. In this study, the authors aimed to evaluate whether FLOW 800 analysis with repeated ICG videoangiography at various stages of
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resection for AVMs is useful for evaluating the hemodynamic changes in AVMs and adjacent brain. To analyze time and fluorescence based parameters, we used quantitative values semiautomatically obtained by applied FLOW 800 software. PATIENTS AND METHODS This study population included 7 patients (3 male, mean age: 33.3 years, range: 9e64 years) who underwent resection of cerebral AVMs between January 2010 and March 2012. Three patients presented with seizures and intracerebral hemorrhages. AVM was incidentally diagnosed in 1 patient. Spetzler-Martin grade I AVM was identified in 2 patients, grade II in 4 patients, and grade III in 1 patient (Table 1).
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Table 1. Patients Characteristics Case
Age (y)/ Sex
AVM Location
S&M Grade
Presentation
Location of Nidus
Maximum Size of Nidus, mm
ICG Injection, Times
Intra- or Postoperative DSA
1
27/F
Lt. parietal
2
Hemorrhage
Superficial
28
5
Yes
2
29/F
Lt. temporal
2
Seizure
Superficial
19
5
Yes
3
34/F
Rt. insula
1
Hemorrhage
Deep
10
5
Yes
4
9/F
Lt. parietal
3
Seizure
Deep
22
5
Yes
5
36/M
Lt. temporal
2
Seizure
Deep
20
6
Yes
6
34/M
Rt. frontal
2
Incidental
Superficial
42
4
Yes
7
64/M
Rt. cerebellum
1
Hemorrhage
Superficial
8
3
Yes
Deep means that nidus is covered by parenchyma and superficial means that nidus faces on the surface of the parenchyma. AVM, arteriovenous malformation; S&M, Spetzler and Martin; ICG, indocyanine green; DSA, digital subtraction angiography; F, female; M, male.
Three patients with deep feeders, which were considered difficult to detect in the superficial operative field, underwent preoperative embolization using N-butyl2-cyanoacrylate. To detect residual AVMs, intraoperative digital subtraction angiography (DSA) was performed in 2 cases and postoperative DSA in 5 cases. ICG Videoangiography After intravenous bolus injection of ICG, the operative field was illuminated by the use of a microscope-integrated light source with a wavelength covering the ICG absorption band (range, 700e850 nm; maximum, 805 nm). Arterial, capillary, and venous flow images were observed on the video screen in real time. The recommended dose of ICG for this type of videoangiography is 0.2e0.5 mg/kg. In this study, all patients received an ICG injection at a dose of 0.1 mg/kg as a bolus. This dose is sufficient for analysis and enables us to perform repeated ICG videoangiography at least 5e10 minutes after the last injection. All images were recorded using the microscopic hardware and could be confirmed easily, immediately, and repeatedly. All operations were performed using OPMI Pentero (Carl Zeiss Co., Oberkochen, Germany). TIMING OF ICG VIDEOANGIOGRAPHY Intraoperative ICG videoangiography was first performed immediately after the dura was opened to analyze baseline flow dynamics of the normal vascular architecture and superficial AVM components. ICG videoangiography was sequentially
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performed to evaluate the flow reduction of the nidus and drainer after the main feeders were occluded by stepwise clipping of the feeders. Finally, ICG videoangiography was performed after total resection of the nidus. FLOW 800 Functions For additionally evaluating blood flow dynamics, a FLOW 800 function was installed in the Pentero microscope. Temporal fluorescence projection uses colors, defined as a color map that allows us to instantly identify the direction and sequence of blood flow. The target vessel is shown as a continuous color scale, depending on the time it takes to reach the ICG dye. Red represents the initial blood inflow, followed by a gradient color scale in blue for the subsequent blood flow sequence. Another map uses different shades of gray based on the maximum fluorescence intensity, which was used for the quantitative analysis of vascular flow dynamics with an ICG intensity-time curve. Management of the Quantitative Analysis of Vascular Flow Dynamics by FLOW 800 Quantitative analysis of vascular flow dynamics was performed as follows: In 1 session, maximum 8 regions of interest (ROIs) were set on a superficial target vessel on the maximum intensity map. Fluorescence intensities were measured in arbitrary intensity units (AIs). Each ICG intensity-time curve and the complementary quantitative values of the time to the half-maximum fluorescence intensity (T1/2 FI [seconds(s)]) from the start of the ICG
analysis, maximum intensity (AI), and fluorescence rate at T1/2 FI (AI/s) were semiautomatically obtained in the same screen, T1/2 FI as “Delay” and fluorescence rate at T1/2 FI as “Slope”. The T1/2 FI by itself has no meaning because the timing taken to start the ICG analysis was not consistent; however, to assess transit time, defined as the time difference between the T1/2 FI in 2 points in the same phase, we evaluated the blood flow dynamics changes in each vascular component. The ROIs were set on the superficial AVM components (main feeders, nidus, and main drainers), cortical artery, and cortical vein adjacent to the AVM. On preoperative DSA, we confirmed that the adjacent cortical artery and the vein surrounding the AVM in the operative field were not associated directly with the AVM. The ROIs of the main feeders and drainers were evaluated at 2 points in some patients when the area of perfusion was apparently different. The ROIs of the cortical artery and vein were evaluated at 1 point in each patient. The total number of evaluated ROIs for the main feeders was 10 (2 points for each case 1, 4, and 5; 1 point for each case 2, 3, 6, and 7), for the nidus was 4 points (1 point for each case 1, 3, 6, and 7), and for the main drainer was 11 points (2 points for each case 1, 2, 5, and 6; 1 point for each case 3, 4, and 7). In 3 patients with a deep-seated nidus, the ROIs could not be set on the nidus because it was covered with parenchyma. The ROIs in each situation were set on the same point. FLOW 800 analysis was performed at the time of dural opening (baseline phase), after maximum flow
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Table 2. The Quantitative Analysis of Maximum Intensity and Fluorescence Intensity Rate at Time to Half-Maximum Fluorescence Intensity (T1/2 FI) in the Timing of Baseline, Postfeeder Clipping, and Final Phase Maximum Intensity (AI)
Fluorescence Intensity Rate at T1/2 FI (AI/s)
Baseline Phase
Postfeeder Clipping Phase
Final Phase
Baseline Phase
Postfeeder Clipping Phase
Final Phase
387.6 252.5
473.7 360.8
420.7 230.6
88.9 103.0
125.1 131.2
90.1 54.4
Cortical vein (n ¼ 7)
260.7 94.5
318.9 147.5
315.7 139.0
40.2 28.6
45.0 23.7
52.6 35.4
Arterial feeder (n ¼ 10)
490.5 249.5
Cortical artery (n ¼ 7)
113.1 88.1
Nidus (n ¼ 4)
520.5 274.5
437.5 283.6
136.5 116.0
114.6 121.3
Draining vein (n ¼ 11)
533.4 271.6
399.8 217.3*
138.1 104.3
271.8 621.4
AI, Arbitrary intensity. *Significantly lower (P ¼ 0.006) compared with baseline phase on draining vein.
reduction of the nidus by stepwise clipping of the feeders (postfeeder clipping phase), and after resection of the nidus (final phase). Quantitative Assessment of FLOW 800 Analysis We evaluated whether FLOW 800 could be used for the quantitative assessment of flow dynamic changes induced by the maximum intensity and fluorescence intensity rate at T1/2 FI in each AVM component (feeder, nidus, and drainer) and cortical artery and vein adjacent to the AVM at baseline, postfeeder clipping, and the final phase. In addition, the transit times between the cortical artery, defined as an index artery, and the AVM components (nidus and drainers), at baseline and postfeeder clipping, were evaluated to confirm the effectiveness of a maximum flow reduction of the nidus by stepwise feeder clipping. Moreover, we compared transit time between the cortical artery and the cortical vein to indicate changes in the cortical perfusion surrounding the AVM during the 3 phases. Statistical Analysis A paired t test was used to compare the quantitative values at paired sites among the baseline, postfeeder clipping, and final phases as appropriate. P < 0.05 was considered statistically significant. RESULTS A total of 33 ICG videoangiographies were successfully performed. The average
number of ICG injections per operation was 4.75 (range, 3e6) (Table 1). FLOW 800 analyses were completely achieved in a few minutes in all patients. Quantitative assessments were achieved in all patients. The calculated maximum intensity and fluorescence intensity rate at T1/2 FI are summarized in Table 2. The calculated transit time from the cortical artery to the nidus, draining vein, and cortical vein during the 3 phases are summarized in Tables 3 and 4. The maximum intensity and fluorescence intensity rate at T1/2 were not significantly different during the 3 phases; however, the maximum intensity of the drainer at the post feeder clipping phase decreased from 533 271 to 399 217 (P ¼ 0.006). After a maximum flow reduction of the nidus by stepwise feeder clipping, transit time between the cortical artery and the drainer was prolonged from 0.08 0.65 seconds to 2.63 1.79 seconds (P < 0.0001). After resection of the nidus, disappearance of the AV shunt to the superficial drainer was
confirmed. Transit time between the cortical artery and the cortical vein reduced from 4.56 1.47 seconds at predissection of the nidus to 3.76 1.37 seconds at postclipping of the feeders (P ¼ 0.024) and 2.63 0.80 seconds at postresection of the nidus (P ¼ 0.005). Total resection of the nidus was confirmed using postoperative DSA in 5 cases and intraoperative DSA in 2 cases. In 1 case, a deep-seated tiny residual nidus with a deep drainer was detected on postoperative angiography just after the operation and was re-resected on the same day. None of the patients experienced an adverse reaction to the ICG dye. No new symptoms or aggravation of neuroradiologic examinations caused by normal perfusion pressure breakthrough occurred. No new permanent deficits caused by the operation occurred. ILLUSTRATIVE CASE A 29-year-old woman who was 25 weeks’ pregnant was admitted because of motor
Table 3. The Comparison of Transit Times Using Half-Maximum Fluorescence Intensity (T1/2 FI) Between Cortical Artery and Nidus and Drainer in the Timing of Baseline and Postfeeder Clipping Phase Baseline Phase, Seconds
Postfeeder Clipping Phase, Seconds
Transit time between cortical artery and nidus (n ¼ 4)
0.30 0.48
1.32 1.52
Transit time between cortical artery and drainer (n ¼ 11)
0.08 0.65
2.63 1.79
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P Value 0.125 < 0.0001
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Table 4. The Comparison of Transit Times Using Half-Maximum Fluorescence Intensity (T1/2 FI) Between Cortical Artery and Cortical Vein in the Timing of Baseline, Postfeeder Clipping, and Final Phase Case
Baseline Phase, seconds
Postfeeder Clipping Phase, seconds
Final Phase, seconds
1
4.36
2.78
1.77
2
3.58
2.53
1.58
3
4.88
4.32
3.16
4
5.97
4.2
2.66
5
2.48
2.64
2.36
6
3.49
3.17
2.74
7
7.13
6.7
4.15
4.56 1.47
3.76 1.37*
2.63 0.80y
Mean
*Significantly faster (P ¼ 0.024) compared with baseline phase. ySignificantly faster (P ¼ 0.005) compared with baseline phase.
transit time between the cortical artery and the cortical vein reduced to 4.36 seconds at predissection, 2.78 seconds at postfeeder clipping, and 1.77 seconds at postresection of the nidus (Figure 2DeI). This reduction possibly indicates an improvement in impaired perfusion in the adjacent tissue surrounding the AVM in the presence of arteriovenous shunts. The maximum intensity and fluorescence intensity rate at T1/2 in each phase were not consistent. Total resection of AVMs was confirmed using ICG videoangiography and postoperative DSA. The patient’s pregnancy was successfully managed, and she vaginally delivered a healthy infant 10 weeks after AVM resection.
DISCUSSION aphasia, right hemiparesis, and right sensory disturbance. Computed tomography revealed intracerebral hematoma in the left parietal lobe (Figure 1A). DSA revealed a left parietal AVM of Spetzler and Martin grade II (Figure 1B). The operation was performed 4 weeks after admission. General anesthesia was conducted with fetal heart rate monitoring. Intraoperative DSA was not performed. After craniotomy and opening of the dura mater (Figure 1C), an initial ICG videoangiography was performed. FLOW 800 analysis was performed, and the ICG intensity-time curve was obtained by setting at 7 ROIs (1 cortical artery defined as the
index artery, 1 cortical vein, 2 main feeders, 1 nidus, and 2 main drainers) on the screen (Figure 2A, D, and G). Similarly, FLOW 800 analysis was performed at postfeeder clipping and postresection of the AVM. After 2 main feeders were clipped, the reduced flow in the nidus and drainer was confirmed by observing the color change (Figure 2B), and transit times between the cortical artery and the nidus, and the 2 main drainers increased to þ1.42, þ1.93, and þ4.39 seconds, respectively (Figure 2E and H). After resection of the nidus, disappearance of the arteriovenous shunt to the superficial drainer was confirmed (Figure 2C), and
Figure 1. Case 1. (A) Computed tomography scan revealed a left parietal intraparenchymal hematoma. (B) Digital subtraction angiography revealed a
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Quantitative Assessment of FLOW 800 Analysis FLOW 800 is an additional analytical imaging tool that can be used to analyze blood flow dynamics. Color maps can help instantly identify the direction and sequence of blood flow by showing a continuous color scale that depends on the time taken by the ICG dye to reach the area. This system is especially intuitive and beneficial for immediately distinguishing between arterial and venous flow, as well as feeders and drainers, because these images are static and in color, compared with those obtained with conventional ICG videoangiography
left parietal arteriovenous malformation of Spetzler and Martin grade II. (C) Intraoperative view using a left parietal approach before dissection.
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Figure 2. Case 1. The analysis of vascular flow during surgery for an arteriovenous malformation (AVM) using FLOW 800. (A) The color map at prefeeder clipping. The AVM components were identified instinctively. (B) The color map at postfeeder clipping. The nidus and drainer became darker, indicating a decrease in the shunt flow. (C) The color map during post-AVM resection. The disappearance of the arteriovenous shunt to the nidus and drainer were confirmed. The regions of interest (ROIs) to analyze flow dynamics using FLOW 800 and the transit times between cortical artery defined as index artery and each component as below. (D) The ROIs at prefeeder clipping. 1, cortical artery; 2, feeder 1a; 3, feeder 1b; 4, nidus; 5, drainer 1a; 6, drainer 1b; 7, cortical vein. (E) The ROIs at postfeeder
(6, 9, 28). In addition to this function, it is possible to analyze the vascular flow dynamics quantitatively with an ICG intensity-time curve. Several studies have demonstrated the usefulness of FLOW 800 to assess the hemodynamic status with quantitative time and fluorescence-based
clipping. 1, cortical artery; 2, nidus; 3, drainer 1a; 4, drainer 1b; 5, cortical vein. (F) The ROIs at post AVM resection. 1, cortical artery; 2, cortical vein. The diagram of blood flow and quantitative values in each ROI (GeI). (G) The numbers 1e7 correspond to the numbers in (D). The color of each number corresponds to the quantitative values of the time to the half-maximum fluorescence intensity (T1/2 FI) on the right side. (H) The numbers 1e5 corresponds to the numbers in (E). The color of each number corresponds to the quantitative values of the T1/2 FI on the right side. (I) The numbers 1 and 2 corresponds to the numbers in (F). The color of each number corresponds to the quantitative values of T1/2 FI on the right side.
parameters in cerebrovascular surgery (14, 15, 17, 20, 24, 29). This quantitative analysis could be helpful especially for the understanding of flow dynamics change at various stages in cerebrovascular surgery (14, 15, 17, 29); however, detailed quantitative analysis has not been established at
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the various stage of resection in AVM surgery. In addition, several parameters using time and fluorescence intensity of FLOW 800 analysis as maximum intensity, time to peak (the time interval between the initial appearance of fluorescence and the maximum fluorescence intensity),
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time to half half-maximal fluorescence, rise time (the interval between 10% and 90% of the maximum fluorescence), blood flow index (the ratio of maximum fluorescence intensity to rise time), and microvascular transit time exist in these studies, and these parameters have not been established. In this study, we used time- and fluorescence-based parameters of T1/2 FI, maximum intensity, and fluorescence rate at T1/2 FI semiautomatically obtained easily and immediately on the screen of the microscope by the applied FLOW 800 software. This is important because this method provides the realtime hemodynamic status of the AVMs and adjacent brain at various stages of resection without complicated calculation. This is first to demonstrate the efficacy of FLOW 800 for the understanding of hemodynamic changes at various stages of resection in AVM surgery. Our quantitative assessments of transit times using T1/2 FI between the cortical artery and each AVM component revealed a decrease in the AV shunt flow after maximum feeder clipping. Flow reduction can be assessed and reassessed at the stage of stepwise feeder clipping when residual main feeder is suspicious by referring to the preoperative assessment. Several ICG injections were made, and maximum flow reduction could be done at this study. These flow pattern changes were only detected by conventional ICG videoangiography to determine the extent of a gradual decrease of ICG dye that passed each AVM component. These quantitative assessments by FLOW 800 provide precise information about a flow reduction of the nidus and drainer. Hashimoto et al. (12) mentioned to the effect of maximum flow reduction of the nidus by stepwise feeder clipping to control intranidal pressure and to avoid uncontrollable bleeding from the nidus and adjacent brain at the early stage of cerebral AVM surgery. Conventional ICG videoangiography can also help identify the flow direction and reduction of AVM instantly; however, this objective information can guide next surgical steps to resect AVMs more safely, effectively, and convincingly, and minimize the sequelae of unanticipated complications. In this study, we also demonstrated the usefulness of FLOW 800 for the assessment of cortical perfusion during AVM surgery. Some authors have reported
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successful analyses in cortical perfusion using ICG videoangiography during decompressive craniectomy for malignant stroke, revascularization for moyamoya disease, surgical obliteration for dural arteriovenous fistula, and subarachnoid hemorrhage (7, 14, 15, 29, 31). In particular, Czabanka et al. (7) reported that the cortical microhemodynamics microvascular transit time (MVTT) increased in patients with moyamoya disease patients compared with that in patients with atherosclerotic cerebrovascular disease and control patients. The MVTT was defined as the time taken for maximum fluorescence intensity from the cortical artery to the cortical vein. The authors specified that the MVTT indirectly represented microvascular blood flow velocity. The transit time Czabanka et al. (7) calculated was similar to the transit time using T1/2 FI in this study; therefore, it is true that the T1/2 FI indirectly represents microvascular blood flow velocity. The problem of their method is that specific software was required to analyze the MVTT; however, it is easy to calculate the T1/2 FI at 2 points in AVMs and surrounding AVM components using FLOW 800 because the T1/2 FI at one point is automatically obtained. Several reports in human and animal models have proven that the local cerebral blood flow surrounding an AVM improves after resection of the AVM by xenon-enhanced computed tomography scan, directional Doppler technique, positron emission tomography, or magnetic resonance perfusion imaging (4, 10, 16, 21, 22, 26, 27). The mechanism underlying low cortical perfusion in the adjacent brain tissues surrounding an AVM involves disturbed cerebral blood flow and vascular reactivity due to the low resistance of the nidus and high flow transnidal shunts (1-3, 27). Furthermore, the impaired cortical perfusion surrounding an AVM improves after resection of AVM. In 1 sulcal AVM case, Kamp et al. (17) suggested that the differences between the arterial and parenchymal fluorescence peaks were longer before than that after occlusion of the AVM, indicating impaired perfusion in the adjacent tissue by arteriovenous shunts. Our results that transit time using T1/2 FI between the cortical artery and vein surrounding the
AVM were shortened after resecting AVMs support this finding. Although the ICG videoangiography for the assessment of cortical perfusion is not fully established, FLOW 800 analysis with transit time may assess the improvement of the impaired cortical perfusion. Study Strengths and Limitations Ng et al. (20) have already described the use of quantitative flow analysis by FLOW 800 during AVM surgery. They showed the mean T1/2 FI and fluorescence intensity rate at T1/2 FI for the arterial feeder, draining vein, and normal cortex in 8 patients; however, these were quantitatively evaluated only at the predissection phase. In our study, we described the dynamic changes in blood flow in each AVM component during surgery and changes in cortical perfusion surrounding the AVM before and after the resection of AVMs using an ICG time intensity curve and revealed that the T1/2 FI parameter was useful for assessing the reduction of AV shunt in the drainers by maximum flow reduction of the nidus and improvement of cortical perfusion in the adjacent brain after resection of AVM. Our study is the first to identify the real-time hemodynamic status of the AVMs and adjacent brain. In this study, we also examined the maximum intensity and fluorescence intensity rate at T1/2 FI, and these parameters did not demonstrate any significant changes during AVM surgery, except for the maximum intensity of the drainer before and after feeder clipping. Several factors, including the dose and timing of the ICG injection, blood pressure, cardiac output, and microscope settings, might influence the results of ICG analysis (17). Because these factors cannot be strictly managed, they might influence the results of the ICG analysis. Kamp et al. (17) indicated that the fluorescence-based parameter such as the maximum intensity and fluorescence intensity rate at T1/2 FI showed large variations, and that they were hard to define, although to minimize variability, the microscope setting, bolus size, injection speed, and ICG injection timing were kept almost the same. On the other hand, they concluded that a timeassociated parameter, such as transit times between 2 points, was subject to less variability to exhibit the perfusion of the cerebral vessels and the cortex. Thus,
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taking our results into consideration, evaluating the time-associated parameter would be more helpful during AVM surgery. The limitation of FLOW 800 analysis is that this technique is only available for superficial AVMs. During surgery, the reduced shunt flow of a deep-seated nidus could be confirmed by a gradual decrease in the superficial drainer’s flow through the nidus when covered with parenchyma; however, when a deep-seated nidus or drainer exists, it is difficult to prove the total resection of AVM by ICG videoangiography (11, 18, 28). Indeed, a deepseated tiny residual nidus with a deep drainer was detected on postoperative angiography and re-resected on the same day in one case in this study. Therefore, we think that intraoperative or postoperative DSA is necessary when deepseated nidus or drainer exists, although there are several limitations as complications, radiation exposure, and additional time in DSA (5, 28). Another study limitation is that the sample size of 7 cases is small, and future studies with more cases are required to provide the assessment of flow dynamics in AVM surgery.
CONCLUSIONS Quantitative assessment of flow dynamics with FLOW 800 using ICG intensity-time curves enabled us to identify the real-time hemodynamic status of the AVMs and adjacent brain easily and immediately during AVM surgery. Time-associated parameter of transit time using using T1/2 FI is useful especially for this assessment. This novel technique facilitates the maximum flow reduction by stepwise feeder clipping and resection of AVMs more safely and convincingly. Intraoperative or postoperative DSA is necessary for the confirmation of total resection of AVMs with deep-seated lesions. REFERENCES 1. Awad IA, Magdinec M, Schubert A: Intracranial hypertension after resection of cerebral arteriovenous malformations. Predisposing factors and management strategy. Stroke 25:611-620, 1994. 2. Batjer HH, Devous MD Sr, Meyer YJ, Purdy PD, Samson DS: Cerebrovascular hemodynamics in arteriovenous malformation complicated by normal perfusion pressure breakthrough. Neurosurgery 22:503-509, 1988.
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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. Received 6 January 2014; accepted 15 July 2014; published online 18 July 2014 Citation: World Neurosurg. (2015) 83, 2:203-210. http://dx.doi.org/10.1016/j.wneu.2014.07.012 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2015 Elsevier Inc. All rights reserved.
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