**3. Intraoperative strategies to detect aneurysm obliteration and parent vessels patency**

## **3.1 Micro-Doppler ultrasonography (MUSG)**

Doppler ultrasonography was first employed to assess cerebral hemodynamics in extracranial arteries. This method was further refined for the transcranial examination of brain vessels [22]. Technological advancements allowed the reduction of the ultrasound probe's size by raising the ultrasonic frequency. Microprobes for the direct examination of small brain vessels were created as a result of further research [23–25].

Before and after the aneurysm clipping, blood flow velocities in the aneurysm sac and the nearby arteries could be measured using intraoperative microvascular Doppler ultrasonography (MUSG). The probe with a 1 mm-diameter pulsed wave mode is used to make the Doppler measurements. In addition, a suction cannula could be used to insert the Doppler probe, thus allowing precise positioning and stability. With an insonation angle of 30 to 60 degrees, the probe is used to examine all exposed arteries close to the aneurysm as well as the aneurysmal sac [26].

MUSG was first described by Lanborde et al. for intraoperative monitoring of large cerebral aneurysms [27]. MUSG has the ability to identify the orientation and hemodynamics of the parent arteries, as well as the vortex flow or thrombus within the aneurysm sac, prior to the positioning of clip. Particularly in large and challenging aneurysm surgery, MUSG monitoring could determine if the aneurysm sac is entirely clipped and whether parent or perforating arteries are stenosed or

accidentally clipped. MUSG can detect all vessels in the Wills circle and its branches, including those with a diameter of less than 1 mm, because of the availability of a high-frequency micro-probe [28].

Bailes et al. [28] investigated the use of MUSG in aneurysm surgery, observing a capability to detect occlusion or stenosis of parent vessels in 31% of cases after clip positioning, and therefore allowing immediate adjusting.

Stendel et al. [26] MUSG discovered a meaningful stenosis of an adjacent artery caused by clip location in 17 out of 90 (18.9%) aneurysms. In addition, 11 out of 90 (12.2%) patients evaluated with Doppler ultrasound showed a predominantly unoccluded aneurysm. In 26 out of 90 (28.8%) patients, the aneurysm clip was repositioned based on the MDUG findings.

In conclusion, the complete closure of cerebral aneurysms and the patency of parent arteries, arterial branches, and main perforators could be documented by intraoperative MUSG, which is safe, rapid, efficient, dependable, and economical tool. In many situations, this method can be utilized safely in addition to other tools to monitor surgical aneurysms, reducing the risk of postoperative cerebral stroke. The limitations of MUSG include its vulnerability to changes in detecting angle and depth, fluid surrounding vessels, and tractor, as well as its inability to detect the aneurysm's back or minute remnant of its neck.

### **3.2 Indocyanine green video angiography (ICG-VA)**

In 1956, the United States Food and Drug Administration (FDA) approved the use of indocyanine green (ICG) dye, a near-infrared (NIR) fluorescent tricarbocya-9 dye, to assess liver and cardiocirculatory functions. Ophthalmic angiography received additional FDA approval in 1975. ICG dye has an absorption and emission peak (805 and 835 nm, respectively) within the "optical window" of tissue, where endogenous chromophores have minimal absorption. After intravenous administration, ICG primarily binds to globulins (1 lipo-proteins) within 1 to 2 seconds. There is typical vascular permeability, and the dye is still intravascular. The liver is the only organ in the body that can excrete the indocyanine green dye, which has a plasma half-life of 3 to 4 minutes. ICG dye should be administered for video angiography (VA) at a dose of 0.2 to 0.5 mg/kg, with a daily maximum dose of 5 mg/kg.

The use of intraoperative NIR VA was first described by Raabe et al. in 2003, where ICG dye was used for intraoperative observation of vascular flow [29]. A light source that has a wavelength covering a portion of the ICG absorption band illuminates the operating field from the microscope (range 700–850 nm, maximum 805 nm). A bolus of the ICG dye is administered via peripheral vein (the standard 25-mg dose dissolved in 5 ml of water), and a nonintensified video camera captures the fluorescence (spectral range 780–950 nm, maximum 835 nm). To exclusively collect ICG-induced fluorescence, ambient and excitation light are blocked using an optical filter. As a result, real-time viewing of venous, capillary, and artery angiographic pictures is possible [30].

Some authors compared intraoperative and postoperative findings on the patency of the parent, branching, and perforating arteries and the clip occlusion of the aneurysm as indicated by ICG-VA, with the standard digital subtractive (DS) angiography. They observed that in 90% of cases, the results of ICG-VA matched those of intra and postoperative DS angiography. In 7.3% of patients, the ICG method failed to detect a modest but hemodynamically insignificant stenosis that was visible on

*Clipping Strategies and Intraoperative Tools to Detect Aneurysm Obliteration and Cerebral… DOI: http://dx.doi.org/10.5772/intechopen.110774*

DS angiography. In three cases, the ICG approach failed to pick up angiographically significant findings. In two of the cases, the missed findings had no clinical or surgical repercussions; in the third, a 4-mm residual neck may necessitate additional surgery. In 9% of cases, indocyanine green VA gave the surgeon useful information about clip repair [30].

In 90% of instances, the results of ICG-VA matched those of intra- and postoperative DS angiography. In 7.3% of patients, the ICG method failed to detect a modest but hemodynamically insignificant stenosis that was visible on DS angiography. In three cases (one hemodynamically important stenosis and two residual aneurysm necks [2.7% of cases]), the ICG approach failed to pick up angiographically significant findings. In two of the cases, the missed findings had no clinical or surgical repercussions; in the third, a 4-mm residual neck may necessitate additional surgery. A substantial amount of information was provided to the surgeon using indocyanine green VA. The authors concluded that ICG-VA using a microscope is easy to perform and gives real-time data on the aneurysm sac and the patency of all diameters of arteries.

Many others studied compared the safety and efficacy of ICG-VA with DS angiography [1, 5, 13, 14, 17, 19, 20, 31, 32].

Ozgiray et al. [5] described that in 93.5% of aneurysms ICG-VA accurately determined vascular patency and aneurysm obliteration; only in 3.6% of cases ICG-VA showed no flow after clipping whereas puncturing the aneurysm's dome indicated residual flow, in 0.9% it demonstrated sustained flow within the aneurysm in one whereas MUSG and puncture of the dome did not, and in 0.9% it failed to show residual neck.

Della Puppa et al. [13] analyzed the role of ICG-VA added to the other techniques, observing that ICG-VA was useful for detecting parent vessels occlusion or residual aneurysm in 8.3% of cases. Moreover, only one false negative remnant neck was noted, with a negative predictive value of 98.8%, and ICG-VA was more sensitive to reveal remnant primarily in atherosclerotic aneurysms (P < 0.05).

In conclusion, ICG-VA represents the best tool to directly observe parent vessels patency and aneurysm obliteration. The surgical microscope's integration and its ability to show perforating arteries with submillimeter widths are two of its distinctive advantages. Its utility during aneurysm surgery is supported by its ease use, rapidity, and high level of accuracy for identifying partially clipped aneurysms and accidentally occluded vessels. Moreover, the ICG-VA has the potential to be more broadly accessible than intraoperative DS angiography.

#### **3.3 Electrophysiological monitoring**

Electroencephalography (EEG), motor evoked potentials (MEPs), somatosensory evoked potentials (SSEPs), visual evoked potentials (VEPs), and auditory evoked potentials are few of the intraoperative neuromonitoring (IONM) techniques available for cerebrovascular surgery. The overall objective of each modality is to improve the patient's functional outcome by detecting changes in brain activity that can indicate possible neurological compromise. Each modality has its own unique applications [33, 34]. Electrophysiological monitoring is useful to observe potential early ischemia during temporary clipping or after permanent clipping, allowing to remove of the temporary clip to restore the flow, or to explore the parent and perforating vessels after permanent clip detecting a possible erroneous clipping [15, 35].

Usually, the motor pathway is monitored by stimulating the motor area using electrodes inserted in C1–C2 (C3–C4) through a train of 4 to 5 stimuli with the intensity of 250 to 500 Hz. The somatosensory pathway is monitored by stimulating contralateral medianus nerve at the wrist for the upper limb SSEPs, and the contralateral tibial nerve at the medial malleolus for the lower limb SSEPs. General anesthesia could affect the results of IONM; thus, total intravenous anesthesia is recommended, possibly avoiding the use of neuromuscular blockers unless absolutely necessary [13, 36].

Knowing the N20 peak's amplitude in relation to the evoked parietal response is crucial. N20 peak amplitude was decreased by more than 50% when compared to its absolute values, indicating a decrease in rCBF values of around 12–16 mL/100 g/ min. This is comparable to cerebral ischemia that may be reversible, however, chronic maintenance of a low rCBF may result in cerebral infarct [37, 38].

Penchet et al. observed a significant reduction of SSEP (more than 50%) in 25.9% of the patients, of which 6.9% with postoperative ischemic stroke and partial or no recovery, 19% with complete recovery, and only two postoperative ischemic strokes. The authors concluded that changes in SSEP had a strong correlation with postoperative stroke incidence [34].

Staarmann et al. [36] described IONM alterations in 15 cases out of 133 clipped aneurysms, including 12 transient changes without new postoperative deficits and 3 permanent changes with new postoperative deficits. Transcranial motor evoked potentials and somatosensory evoked potentials predicted 2 and 1 of the postoperative deficits, respectively. Moreover, they observed only 1.1% incidence of IONM alterations and permanent neurological deficits associated with temporary clipping [36].

Della Puppa et al. [13] observed a reduction of evoked potential in 11 patients during temporary or permanent clipping, 10 in accordance with MEPs, and 1 in accordance with SSEP. All these IONM normalized after temporary clip removal or permanent clip repositioning. MEP was significantly correlated with proximal located aneurysm (ACoA, ICA, M1).

In conclusion, multimodal IONM is very sensitive and specific for identifying new deficits. The early detection of potential reversible ischemia allows maneuvers such as temporary clipping removal or the identification of another component (such as releasing brain retraction or reposition of permanent clip) to lower the likelihood of postoperative complications.

### **4. Future perspectives**

ICG-VA represents the most dominant innovation of the latest years for the surgical treatment of brain aneurysms. Future technological advances should potentially allow to facilitate three-dimensional (3D) orientation, optimize clip placement, and manage the proximal and distal control [39].

One of the first considerations that it could be done about future advances in vascular neurosurgery is that brain aneurysm surgery represents a specific technical challenge for young neurosurgeons, due to the huge increase in endovascular technology in the latest years. Since endovascular treatments continue to develop, a similar focus on technological innovation in open surgical repair should be implemented, for patients to continue to benefit from whichever treatment option is most effective for their aneurysm. Thus, training in this subspeciality of neurosurgery represents an increasing challenge in the modern era and a specific field that applies to increased

#### *Clipping Strategies and Intraoperative Tools to Detect Aneurysm Obliteration and Cerebral… DOI: http://dx.doi.org/10.5772/intechopen.110774*

learning opportunities [40]. High-fidelity surgical simulators may provide a partial answer by enabling surgeons to gain expertise. In fact, preoperative simulation tailored to the patient who will be operated, as well as 3D models**,** could be detrimental to compensate for the lack of opportunities to learn vascular surgery, leading young neurosurgeons to an easier improvement of technical skills, thus facilitating 3D orientation and optimizing the management of surgical procedures [41].

Another issue to be considered regarding future advances is the identification of technologies that would improve clip application (e.g., advances in applicators, advances in clips) and intraoperative visualization (e.g., endoscopes and intraoperative imaging). Endoscopes are not usually included in the aneurysm surgical workflow, but they could improve the visualization of aneurysm "blind spot**",** facilitating aneurysm management and 3D orientation [39].

Hybrid operating theaters, which include intraoperative CT scans and intraoperative angiography, are not very diffused. Still, they should be identified as potential future advances to optimize clip application and 3D orientation, increasing the safety of aneurysm obliteration and neck reconstruction, reducing surgical morbidity despite of the reduced surgical cases compared to the past.

In conclusion, the majority of future advances in vascular neurosurgery should be targeted to optimize clip application and improve 3D visualization and orientation, for example, increasing the use of endoscopic-assisted surgery, implementing the development of surgical simulators, and investing in the growth of hybrid openedendovascular technique thanks to hybrid operating theaters [39].

## **5. Conclusions**

Microsurgical obliteration of cerebral aneurysms represents the best long-term treatment for this pathology. Despite high surgical expertise, aneurysm surgery is often associated with an increased risk of intraoperative rupture. For this reason, vascular control is pivotal and should be aimed at by the neurosurgeon during aneurysm surgery. The application of single or multiple definitive clips on the neck of the aneurysm can be achieved with different techniques in order to arrest the blood flow into the dome [12]. Intraoperative use of ICG-VA, MUSG, and IONM can effectively reduce brain tissue ischemia ad morbidity after clipping intracranial aneurysm, thus improving the surgical outcome. Microsurgical clipping with the use of a multimodal monitoring method led to a high incidence of aneurysm exclusion with little morbidity [13].
