**1. Introduction**

Usually, arteries in the human body have 3 layers of tissue called, from the vascular lumen to the outermost layer, the intima, media, and adventitia, respectively. The intima is composed of an endothelial tissue layer, which has direct contact with

intraluminal blood, and a subendothelial layer, formed by connective tissue. The internal elastic lamina, a layer of elastic fibers, separates the tunica intima from the tunica media. The media is basically formed by concentrically organized smooth muscle fibers and collagen fibers, in which type III collagen predominates. The external elastic lamina separates the tunica media and adventitia, typical in arteries throughout the body but absent in intracranial arteries. Finally, the adventitia is mainly formed by a complex network interspersed with type I collagen, elastin, fibroblasts, nerves, and vasa vasorum. Therefore, the wall of the cerebral arteries has a different structure from other extracranial arteries, with a scarce adventitia and a low proportion of elastic fibers. Furthermore, they are immersed in the cerebrospinal fluid of the subarachnoid space instead of the surrounding connective tissue [1, 2].

In normal arteries, myointimal hyperplasia is an adaptive physiological reaction to hemodynamic stress or to a mechanism of vascular injury, resulting from a change in the phenotype of smooth muscle cells in the tunica media, which promote their migration and proliferation, outlining the lesion endothelium [3]. Once the molecular mechanisms become unable to compensate for the myointimal injury, cellular and humoral inflammatory responses are triggered (mainly responsible for aneurysm formation) [4–6], and responses mediated by inflammatory cytokines, such as tumor necrosis factor (TNF).), interleukin-β (IL-1β) and matrix metalloproteinases (MMPs), which promote macrophage influx and continuous degradation of collagen and elastin fibers [6–9]. IA is, therefore, an encephalic vascular lesion characterized by an abnormal dilation of the blood vessels of the brain, affecting, in general, about 5% of the population [7, 10–13], resulting from a molecular and hemodynamic imbalance, the which would explain its formation in arterial junctions and bifurcations, where an excess of hemodynamic stress is exerted on the vessel wall, followed, then, by a local inflammatory process that leads to disruption of the internal elastic lamina [14–17].

Once the IA ruptures, blood leaks into the subarachnoid space, the natural space between the arachnoid mater and the pia mater, producing spontaneous subarachnoid hemorrhage (SAH). It is an entity with high mortality, reaching 50% of affected individuals, and considerable morbidity among survivors. It is noteworthy the fact that approximately 30% of subarachnoid hemorrhages resulting from intracranial aneurysm rupture occur during sleep. This denotes a multifactorial pathophysiological nature fundamentally related to inflammation and not exclusively hemodynamic, since in this period hemodynamic stress tends to be less intense than during the day. In the natural history of IA there are known modifiable and non-modifiable risk factors for rupture. As an example of the former, we can mention smoking and high blood pressure. Non-modifiable factors include advanced age, genetic profile, and family history of SAH, growth of the aneurysmal sac, among others [7, 13].

Bouthillier and van Loveren's classification (**Figure 1**), separates the internal carotid artery into segments according to its branches and anatomical relationships with adjacent structures. This makes it possible to classify carotid saccular ais according to these segments and their respective vessels. Thus, IA's can be in the cavernous, clinoid, ophthalmic and/or posterior communicating segments of the carotid artery and are primarily related to an arterial branch of the carotid artery or to an anatomical structure of interest.

As for the paraclinoid IAs, specifically, since 1968 with the work of Drake et al. [18], anatomical patterns are studied to try to classify them. However, until today we find confounding factors that add difficulty in understanding these classifications. Much of this stems from the fact that the existing nomenclature of aneurysms *A New Paradigm: How to Study the Exact Location of a Paraclinoid Aneurysm… DOI: http://dx.doi.org/10.5772/intechopen.110492*

#### **Figure 1.**

*Anatomical structure of the internal carotid artery (ICA). Segments: petrous (C2), lacerus (C3), cavernous (C4), clinoid (C5), ophthalmic (C6), proximal and distal dural rings, III cranial nerve and cavernous sinus. By the classification of Bouthhillier and van Loveren. On the left, schematic drawing and on the right, a piece obtained through anatomical dissection (adapted from Boutillier and Van Loveren left and right anatomical dissection by Hugo Doria, MD PhD).*

arising from the clinoid and ophthalmic segments of the ICA is contradictory, mainly for anatomical reasons [19, 20]. First: the ophthalmic artery can arise both from the clinoid segment (C5) and from the ophthalmic segment (C6) [21] of the ICA as previously exposed [12, 19]. Second: aneurysms in this region do not necessarily arise in relation to a named arterial branch [19, 20]. Third: aneurysms in this area can be intradural, extradural or transitional and sometimes it is impossible to make this determination using radiographic investigations currently available [20]. Fourth: the recognition of the carotid cavum as an entity further complicated the issue, as cavum aneurysms are located below the plane of the distal dural ring (DDR), but are intradural [20, 22, 23]. In a summarized and practical way, the proposed classifications try to establish some standard for the surgical technique, always in search of the basic principles of the management of cerebral aneurysms, regardless of their location (establishing proximal and distal vascular control; adequate exposure of the neck and complete obliteration of the aneurysm with maintenance of cerebral blood flow distal to the aneurysm) [23].

Paraclinoid aneurysms are lesions that originate in the cavernous, clinoid, or ophthalmic segments of the ICA, defined by Bouthillier as segments C4, C5 and C6, respectively (**Figure 2**).

These are aneurysms that may arise proximally to the proximal dural ring (PDR), between the dural rings or distally to the DDR, between the distal dural ring and the posterior communicating artery and may be intra or extracavernous. Extracavernous paraclinoid aneurysms present a risk of SAH and usually require treatment, while unequivocally intracavernous aneurysms are located completely below the proximal

#### **Figure 2.**

*A - Angiography with digital subtraction in the AP showing a large multi-lobulated paraclinoid aneurysm with a medial conformation. B – Microsurgical image of the same aneurysm after anterior intradural clinoidectomy. 1 – Optic Nerve, 2 – Aneurysm, 3 – Left Carotid Artery, black arrow – emergence of the ophthalmic artery (angiography and microsurgical photography kindly provided by Sergio Tadeu Fernandes, MD PhD).*

dural ring, rarely coursing with SAH and present lower morbidity than aneurysms originating from the intradural space [24].

Approximately 33–59% of paraclinoid IAs are associated with the ophthalmic artery; 27–47% are associated with the superior hypophyseal artery and between 14% and 20% are not associated with any arterial branch. Paraclinoid IAs comprise between 1.4% to 9.1% of all ruptured aneurysms [25].

They are considered uncommon, accounting for approximately 5% of IAs, reaching up to 14% of IAs, in some studies, with an increased prevalence in women [26–28]. These aneurysms affect the ICA between the cavernous segment and the origin of the posterior communicating artery.

As for the diagnosis, the available methods are classified as invasive and noninvasive. The invasive method is digital subtraction angiography (DSA) performed in a hemodynamic suite through selective arterial catheterization of the intracranial vascular tree, which allows, in addition to the structural study, the analysis of hemodynamic behavior in real time. Despite being invasive and with intrinsic risks, this method is still consolidated as the gold standard for this purpose [29, 30]. On the other hand, non-invasive methods include the use of images processed by computer graphics and three-dimensional reconstructions obtained by Computed Tomography (CT-Angio) or Magnetic Resonance (MR-Angio) devices that are increasingly sensitive and specific, often used not only as screening, but replacing DSA in selected cases with the additional benefit of contributing, not only with the visualization of the target pathology, but its relationships with adjacent structures, such as the anterior clinoid process [31, 32].

However, despite all the technological advances and modern imaging techniques validated so far, both by invasive and non-invasive methods, paraclinoid aneurysms still represent a separate challenge. In view of the difficulty in determining whether the aneurysm studied is located exclusively in the cavernous compartment of the carotid artery, or whether it has a relationship, even if partial, with the subarachnoid space. The practical significance of such information is that each type of aneurysm requires a different surgical strategy. Aneurysms identified as being completely intradural may not require anterior clinoidectomy. On the other hand, transitional aneurysms may require a wide opening of the dural rings and adequate management of the roof of the cavernous sinus. Still, those located completely in the intracavernous space

#### *A New Paradigm: How to Study the Exact Location of a Paraclinoid Aneurysm… DOI: http://dx.doi.org/10.5772/intechopen.110492*

rarely require any kind of approach. Until then, it was only possible to determine this exact relationship through microsurgical exploration.

Many strategies have emerged with the purpose of resolving this dilemma. The proposal to use the origin of the ophthalmic artery as a marker for the intradural ICA, making a distinction between the intra and extradural segments, had some relevance, but it was soon found that this anatomical marker had low accuracy, since the origin of the artery Ophthalmic is extradural, that is, proximal to the distal dural ring, in 2–16% of cases [11, 12, 19, 23, 33–35]. There was a proposal to use the base of the ACP in lateral radiographs, serving as a more reliable marker than the origin of the OphA in angiograms, which also proved to be of low accuracy because, for example, carotid cavum aneurysms can be observed below the level of the ACP and, even so, they are inside the intradural space. Subsequently, Oikawa *et al.* [36] proposed that the use of the anterior clinoid process (ACP) in lateral projection radiographs should be replaced by the sellar tubercle in the same projection, when evaluating aneurysms on the medial side of the dural ring, as this is more proximal than the lateral one [36]. Kim *et al*. stated that they were not aware of any combination of radiographic exams that allowed the reliable identification of the distal dural ring, reaffirming that "surgical exploration is the only solution in these cases" [19]. In 2001, Murayama *et al.* proposed the use of 3D CTA as an indirect method for identifying the distal dural ring, noting that in 84.8% of the evaluated images it was possible to identify a concave impression on the anterior curve of the ICA and suggested that this concavity coincides with the location of the distal dural ring, because of ring fixation to the ICA [37]. Gonzalez *et al.* postulated that, if the optic pillar could be reliably identified with high-resolution CTA, it could represent an anatomical landmark for evaluating aneurysms in this critical region [24]. Hashimoto *et al.* applied the same methodology for analysis of the optical pillar, through CTA images, comparing images and intraoperative findings and stated that the optical pillar is the most useful landmark for operative planning of aneurysms in this region [38].

With the purpose of changing the indirect reference of the dural rings previously studied by previous methods, magnetic resonance imaging (MRI) begins to be used for direct visualization of the distal dural ring and the limits of the cavernous sinus in relation to paraclinoid aneurysms. However, the method initially ran into difficulties such as low spatial resolution and the need to improve signal acquisition powers. Thines *et al.* proposed the improvement of the resolution in 3 Tesla weighted in T2, demonstrating in thin and contiguous sections, the dural folds of the roof of the cavernous sinus and the distal dural ring, however, they were not compared with surgical findings or post-mortem dissections [39, 40]. In 2019, Obusez *et al.* evaluated the use of MR imaging of the vessel wall ("VW-MR") to determine the exact location of unruptured paraclinoid aneurysms in relation to DDR but, once again, the study ran into low statistical power and there was no comparison with surgery or necropsy study to verify the findings [41]. Therefore, until now, there is no knowledge of accuracy studies for the diagnostic tests of paraclinoid aneurysms and their relationship with the cavernous sinus. The studies found are series of cases that did not determine sensitivity, specificity, predictive values, and likelihood ratios [24, 37–40, 42–46].

Therefore, the preoperative identification of the distal dural ring and the actual definition of the limits of the roof of the cavernous sinus in relation to paraclinoid aneurysms remains an unresolved problem. This dilemma stimulated the studies of the authors of this chapter to develop more adequate preoperative evaluation protocols and proposed the adequate formatting of 3-tesla MRI studies with sensitivity and specificity sufficiently capable of determining the exact location of these AI in relation to the cavernous sinus, the which allows an effective diagnosis and enables a more adequate, safe, and efficient surgical planning. Next, we will describe the formulation of these protocols of great interest for neuroradiological and neurosurgical practice.
