Indocyanine Green and Cerebral Revascularization

20 Indocyanine Green and Cerebral Revascularization

Lars Wessels, Nils Hecht, and Peter Vajkoczy

Abstract
Maintenance of cerebral blood flow is essential to prevent cerebral ischemia. In 10% of ischemic stroke patients, cerebral bypass surgery may be considered to treat chronic occlusion of the cerebral vasculature due to arteriosclerosis or moyamoya vasculopathy. In other situations, grafting of an interposition bypass may be needed to treat complex intracranial aneurysms or skull base tumors that require sacrifice of the main vessels supplying blood to the brain. However, flow augmentation or flow replacement by grafting of an intracranial to intracranial (IC-IC) or extracranial to intracranial (EC-IC) bypass is naturally also associated with an intraoperative risk of ischemic stroke or bypass failure, which may result in neurological deficits or even death. For this reason, immediate intraoperative control of bypass patency and function is required. Besides intraoperative digital subtraction angiography as the gold standard for bypass patency control, simpler and safer methods for immediate intraoperative assessment of bypass patency have been developed and implemented in recent years. Here, indocyanine green videoangiography has been validated as a reliable, cost-effective, and easy-to-use tool for immediate real-time visualization of bypass patency and cerebrovascular hemodynamics.

Keywords: indocyanine green, bypass, cerebral revascularization, cerebral bypass surgery, cerebral aneurysm, moyamoya, chronic cerebral ischemia, cerebrovascular disease, stroke

20.1 Introduction

Mainly two general indications for direct cerebral revascularization exist: (1) chronic hemodynamic compromise with the need to augment cerebral blood flow and (2) the need to replace blood flow completely following sacrifice of vessels that maintain cerebral blood flow (CBF) for treatment of complex vascular lesions or tumors of the skull base.

In both cases, positive and certain intraoperative assessment of bypass patency is essential, particularly following sacrifice of large vessels where bypass occlusion would result in ischemic stroke. To prevent this complication, intraoperative visualization of the cerebral vasculature is crucial. Therefore, additional visual information is necessary regarding blood flow in the recipient vessel, bypass patency, and blood flow in the bypass to estimate its performance. The following chapter provides an overview about the history, pitfalls, and pearls of intraoperative angiography by indocyanine green videoangiography (ICG-VA) during cerebral revascularization.

20.2 ICG as a Tool for Quality Control in Cerebral Revascularization

ICG was first described in 1975 by Flower and Hochheimer as a tool for angiography of the retina in ophthalmology.1 In 2003, ICG-VA was then introduced in vascular neurosurgery for noninvasive, angiographic real-time visualization of blood flow in the superficial vasculature of the brain.² The first technological ICG-VA setup was relatively complex in handling and consisted of a separate camera. In addition, analysis of the transit time of the fluorescent dye within the vasculature had to be done manually. Despite this initial workflow limitation, however, ICG-VA was a great advantage over intraoperative digital subtraction angiogram, mostly due to its low risk profile, simple handling, cost and time efficiency, and the fact that the procedure could be performed and interpreted by the surgeon without the need for radiological and/or neuroradiological assistance. Meanwhile, workflow and handling were significantly improved by routine integration of ICG-VA into the surgical microscope and more recently, a new software tool named FLOW 800 was introduced that allows immediate color-coded visualization and pseudo-quantitative analysis of the temporal distribution dynamics of the fluorescent ICG dye.³

In general, ICG-VA and FLOW 800 are based on the fluorescent properties of ICG, allowing angiographic visualization of flow through the vasculature within the imaging field of the surgical microscope. After intravenous injection of the dye (0.3 mg/kg body weight [25 mg dissolved in 2.5 mL water]),⁴ the ICG-VA filter is activated by pushing a button on the handle of the surgical microscope, which activates an infrared laser light illumination (780-nm wavelength) together with a registration of the emitted light by a camera with a specific filter for the ICG absorption and emission peaks of 805 and 835 nm, respectively. The obtained images are recorded in black and white as a movie and played back and projected into the visual field of the surgical microscope. The mean rise time of fluorescent intensity after injection is 5.2 seconds and time to peak is 9.4 seconds. The half-time fluorescent intensity is around 20 seconds but depends on the cardiac output and on the blood flow in the vessel.^5,6 The fluorescence of the ICG dye is nonlinear to its concentration and doubles when the concentration increases 10-fold. The ICG dye remains intravascularly if there is no vascular leakage.⁷ The injection can be repeated during one operation after an interval of 15 minutes.⁸ ICG is not metabolized in the body. After systemic administration, it binds to a transport protein (glutathione S-transferase) and has no known interactions or modifications before its excretion into the bile juice with a plasma half-life of 4 minutes.⁹

The ICG-VA technique is very easy to perform, but there are some pitfalls that need to be avoided. First, intravenous application should be performed with standard intravenous access. Central venous injection will lead to much faster distribution into the cerebral vessels. Furthermore, the speed of the injection and the amount of fluid administered after injection of the dye can lead to significant variations of the time-to-peak fluorescence during surgery. Due to its systemic application, the cardiac output has influence on the ICG dye distribution. Atrial fibrillation and cardiac insufficiency can prolong the time to signal. In case of a missing signal after injection, possible extra-vessel injection should be checked for and fresh dye should be re-injected due to its instability from light exposure.

Apart from visualizing the patency of perforating arteries following aneurysm clipping, confirmation of the patency of an extracranial to intracranial (EC-IC) or intracranial to intracranial (IC-IC) bypass remains one of the key indications for ICG-VA. Mainly, this is because ICG-VA ensures quality control and patient safety during bypass surgery through immediate visualization of intravascular blood flow, providing the vascular neurosurgeon with relevant information extending simple patency control.

With a superficial temporal artery to middle cerebral artery (STA-MCA) bypass, visualization of blood flow and semi-quantitative information about local cerebral perfusion and vessel diameter can help find the right target vessel in the sylvian fissure.8,10,11 This together with a standardized approach based on anatomic landmarks can optimize postoperative results regarding bypass patency.¹² Further, ICG is not able to penetrate the intact blood–brain barrier (BBB). Due to this property, ICG-VA visualizes disrupted or impaired BBB in ischemic areas or surrounding pathological vessels, as demonstrated in patients with ischemic stroke.^7,8

The FLOW 800 software provides color-coded visualization of hemodynamic parameters during surgery. This allows a comparative assessment of changes within the micro- and macrocirculation before and after revascularization ( Fig. 20.1).⁶ However, it should be noted that several confounding factors exist that may influence the hemodynamic readout of FLOW 800, such as the speed and route of intravenous injection or the circulation time depending on the cardiac output.⁵ Consequently, FLOW 800 is not intended to measure perfusion directly or in a continuous fashion and therefore, the ICG-VA-based semi-quantification of the mean transit time of the fluorescent dye should mainly be used for an arbitrary estimation of relative flow velocity, ideally in a before-and-after setting. To further ensure graft patency, quantitative information on flow within the bypass graft as well as semi-quantitative information on cortical tissue perfusion can be intraoperatively obtained by perivascular ultrasonic flow measurements¹³ and laser speckle imaging.^14,15 However, the ICG-based analysis of blood flow after revascularization can help estimate the specific risk for postoperative hyperperfusion syndrome and may help provide these patients with intensified blood pressure monitoring after surgery.⁷ In addition, the diameter of the vessel wall can be estimated with ICG-VA, because ICG only fills the lumen of the vessel and this can be subtracted from the vessel diameter under white light, which may help determine the grade of atherosclerosis or find pathological thin areas in the vessel wall with increased risk for insufficient anastomosis.¹⁶ Lastly, ICG before craniotomy can help visualize the frontal branches of the middle meningeal artery in one-third of moyamoya patients before STA-MCA bypass surgery and helps preserve these vessels, a potential benefit if additional indirect revascularization is planned.¹⁷

Still the most important role of ICG-VA in cerebral revascularization is control of bypass patency during surgery. ICG-VA provides direct control of bypass patency during surgery and enables the surgeon to directly revise the anastomosis if it shows no optimal patency. This helps prevent early graft failure and ICG-VA can help identify the point of occlusion (Video 20.1).^4,18 One problem with ICG-VA is the inability to visualize the surrounding tissue. The monochrome gives no information about surrounding structures, which may lead to difficulties, especially in challenging anatomical situations. A new technology might be helpful in solving this problem by using dual-image videoangiography in addition to conventional ICG-VA, providing the surgeon with a white-light picture overlaid by the ICG-VA signal. This allows direct integration of the fluorescent signal into the anatomical structures.

20.3 Indocyanine Green in Different Bypass Indications

The need for intraoperative visualization of bypass and brain vessels is essential for various bypass techniques, although different aspects are important among different techniques and indications.