**2. Original studies that define the precise anatomical relationship between the intradural and intracavernous compartments applied to the context of paraclinoid aneurysms**

### **2.1 Method based on 3t MR images compared with 3D models, anatomy in cadaveric and microsurgical specimen**

This method documented the correlation between the oculomotor nerve and the internal carotid artery, assuming their intersection, visualized in a 3 T magnetic resonance study and confirmed from printed three-dimensional biomodels and microsurgery, as a new anatomical-radiological paradigm that marks the upper limit of the cavernous segment of the internal carotid artery, distinguishing paraclinoid intracranial aneurysms. This is a retrospective study carried out in four stages: anatomical, radiological, 3D printing stage and surgical stage. The internal carotid arteries were dissected in their clinoid topography of 10 cadaveric specimens, totaling 20 cerebral hemispheres. Magnetic resonance images and 3D biomodels of 42 aneurysms from 34 patients were analyzed [47].

Magnetic resonance imaging and MRI angiography were performed in a 3 Tesla (3 T) (Siemens-Skyra Evolve, Erlangen, Germany) and GE (GE Health care, HDXT, Milwaukee, USA) machine using a 32- and 8-channel dedicated skull coil, with the objective of identifying the course of the III nerve when crossing laterally with the ICA, inferring at this point the presence of the carotid-oculomotor membrane and correlating this point to the paraclinoid aneurysm under study (**Figure 3**).

High-resolution images were acquired, following the established protocol, in 2D Coronal T2 Fast Spin Echo (FSE) sequences with thin sections, intracranial arterial magnetic AngioMRI in the 3D TOF technique with and without gadolinium, for vascular analysis. The detailed protocol of imaging studies can be found in [47].

The following structures were analyzed: Identification of the internal carotid artery ICA, identification of the oculomotor nerve in all its extension. Identification of anatomical repairs - Anterior Clinoidal Process (ACP), Ophthalmic Artery (OphA), Optic Nerve (ON), Optical Strut (OS), Diaphragm Sellae (DS); Identification of the paraclinoid aneurysm in the patient under study and the relationships of its neck and dome with the III cranial nerve. The intersection between the internal carotid artery (ICA) and the III nerve was identified on CORONAL T2 / CORONAL FIESTA / volumetric T1 with intravenous contrast and post-gadolinium AXIAL 3D TOF sequences.

According to their relationship with the III nerve, paraclinoid aneurysms were classified as follows: Superior to the superior border of the III nerve, whose neck and dome are located distal to the intersection ICA X ON, in an extracavernous location; at the level of the superior border of the III nerve or in a transitional location (with a part of the aneurysmal neck or dome located superiorly and another part inferiorly to the superior border of the ON in its intersection with the ICA); and inferior to the upper border of the oculomotor nerve, in an intracavernous location, when the aneurysm neck and the dome are located below the ICA x III nerve intersection.

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

#### **Figure 3.**

*(A) Bilateral identification of NO on 3 T MRI in T2, coronal sections. In this section, both ONs are contained in the interpeduncular cistern between the posterior cerebral artery, superiorly, and the superior cerebellar artery, inferiorly. We used this cut to begin following ON on its path from the midbrain to the cavernous sinus, in view of the ease with which ON could be identified without a doubt. (B) Location of ON (yellow arrows) and ICA (red arrows) left and right, on 3 T MRI T2 sequence coronal thin slices. Emphasis on the cerebrospinal fluid cistern adjacent to the ON, halo of hypersignal provided by the cerebrospinal fluid, circumcising the ON in the imminence of its entry into the posterior roof of the cavernous sinus, in the topography of the ON triangle. (C) Location of ON (yellow arrow), ICA (red arrow) and left AI (orange arrow) on 3 T MRI in T2 sequence, axial view. Again, emphasis on the halo provided by the cerebrospinal fluid circumcising the ON, a cistern adjacent to the ON, exactly on the verge of its entry into the posterior roof of the cavernous sinus, within the ON triangle. We used this cistern as a marker to identify cranial nerve III in its path from posterior to anterior, in its transition from the cisternal portion (posterior) to the intracavernous portion (anterior). (D) Identification of ON (yellow arrow) at its intersection with the paraclinoid ICA (red arrow) in the cavernous sinus. The ACP (blue arrow) can be seen just above the NO. The dashed line connecting the upper border of the ON, laterally, to the ICA, medially, is used for evaluation and classification of the AI under study, classified as superior or extracavernous in this image – the entire neck of the aneurysm is found above the upper border of the ON. Caption: ICA – internal carotid artery, NO – oculomotor nerve, ACP – anterior clinoid process, OphA – ophthalmic artery, ON – optic nerve, OS – optic strut, DS – diaphragm sellae, IA – intracranial aneurysm, CSF – cerebrospinal fluid (images kindly provided by Dr. Hugo Doria, MD PhD [47]).*

To obtain the 3D model, it was necessary to compile Computed Tomography (CT) and 3-tesla Magnetic Resonance images and computational processing for conversion into STL format (STereoLithography – Stereolithography or triangular pattern language - 3D file of the region of interest). These data were downloaded to the 3D printer, which deposited the chosen material layer by layer, thus forming the desired object on a scale of 140% of the original size for a better visualization of the structures (**Figure 4**).

Of the 34 patients participating in the study, with a total of 42 intracranial aneurysms, 20 patients, totaling 23 aneurysms, underwent intracranial vascular microsurgery for clipping the paraclinoid aneurysm. In the comparative analysis between the

#### **Figure 4.**

*3D biomodel made from radiological images of patients, showing the structures: ICA – internal carotid artery, printed in red; IA – intracranial aneurysm, printed in black; NO – oculomotor nerve, printed in yellow; bone at the base of the skull, printed in white. In A: evidence of IA classified as extracavernous or greater than the upper limit of the ON at its intersection with the ICA. In B: evidence of IA classified as intracavernous or inferior to the upper limit of the ON at its intersection with the ICA. In transparent acrylic, the supports for supporting the anatomical structures in their exact anatomical positions after three-dimensional printing were printed (images kindly provided by Dr. Hugo Doria, MD PhD [47]).*

radiological study and the 3D model of these 42 cases, 40 (95.23%) were considered compatible and of these, 36 (90%) obtained total compatibility in the 3 (neuroradiologist 1 / neuroradiologist 2 / 3D biomodel) evaluations and classifications and 4 (10%) obtained compatibility between 2 of the 3 evaluators (neuroradiologist 1 or neuroradiologist 2 compatible with the 3D biomodel), and the three-dimensional biomodel is the parameter of success in view of its total accuracy and anatomicalradiological reliability (**Figure 5**).

The results together indicate that, in the impossibility of directly identifying the ADP, the identification of the upper limit of the III cranial nerve immediately lateral to the ICA, in all its diameter, and the distance between the III cranial nerve and the ICA can be considered a landmark for delimitation of the roof of the cavernous sinus distinguishing intracavernous ICA and extracavernous ICA since the measurements were close both in the 20 brain hemispheres dissected in 10 anatomical specimens (average distance of 1.19 mm - ranging from 0.6 mm to 1.7 mm) and in the 34 patients studied radiologically (average distance of 1.09 mm - ranging from 0.4 mm to 2.6 mm).

Of the 42 aneurysms studied, twenty-three (54.76%) underwent intracranial vascular microsurgical treatment by clipping, which confirmed the classification of the aneurysm as extracavernous, corroborating the findings in the anatomical specimens and in the radiological analyzes and printed 3D biomodel and indicated that the distance between the III cranial nerve and the ICA can be a landmark for delimiting the ceiling of the cavernous sinus, distinguishing intracavernous ICA and extracavernous ICA.

In summary, in cadaveric specimens, totaling 20 cavernous sinuses studied, we identified that the upper limit of the cavernous sinus is determined by the carotidoculomotor membrane (COMM), which closely correlates to the intersection between the internal carotid artery and the oculomotor nerve, crossing it, transversely across its entire diameter.

Corroborating the anatomical step, we identified the intersection between the oculomotor nerve and the internal carotid artery in 3 Tesla brain magnetic resonance images of 42 aneurysms. The intersection between the oculomotor nerve and the internal carotid artery was established as a new anatomical-radiological landmark for paraclinoid aneurysms in terms of the carotid segment in which they are contained, intra or extracavernous; The 3D biomodel confirmed the radiological precision for the *A New Paradigm: How to Study the Exact Location of a Paraclinoid Aneurysm… DOI: http://dx.doi.org/10.5772/intechopen.110492*

#### **Figure 5.**

*Comparison between the classification of paraclinoidal aneurysms by the two neuroradiologists, in a blind and independent manner, and the classification by the printed three-dimensional biomodel. The radiologists, blindly and independently, classified the aneurysms according to their relationship between the aneurysmal neck and the intersection between the ON and the ICA, as superior, transitional, or inferior to the superior limit of the III cranial nerve, while the author of the work classified the aneurysms based on the processing of CT, MR and Angio RM 3 Tesla images and analysis of the three-dimensional biomodel from the 3D printing (Modification and Publication authorized by Dr. Hugo Doria, MD PhD [47]).*

exact location of the paraclinoid aneurysms, showing high compatibility for the location of the analyzed paraclinoid aneurysms. The surgical procedure performed in 23 aneurysms confirmed this legend and allows formulating a new paradigm for classifying paraclinoid aneurysms, between: extracavernous or superior, intracavernous, or inferior, or transitional in the preoperative stage, thus avoiding surgical exploration and its associated risks.

#### **2.2 Method based on 3t MR images compared with microsurgical anatomy**

This is a cross-sectional clinical study of diagnostic accuracy that analyzed a prospective cohort of 20 patients totaling 25 paraclinoid aneurysms in a single hospital center in São Paulo in the period between 2014 and 2018 [48].

The patients underwent Cerebral Angiography with Digital Subtraction, which characterized the sample with 10 cavernous and 15 non-cavernous aneurysms, as shown in the table below (**Table 1**).

The same sample of patients underwent a 3-tesla MRI study with the specific protocol detailed in [48]. The following structures were analyzed: distal dural ring (DDA); proximal dural ring (PDR); Anterior Clinoid Process (ACP), ICA, Ophthalmic Artery (OphA), Optic Nerve (ON), Optic Strut (OS), Diaphragm Sellae (DS); identification of the paraclinoid aneurysm and the relationships of its neck and dome with adjacent structures. DDR has been identified as the reflection of the dura mater surrounding the ICA as it leaves the roof of the cavernous sinus. It is contained in a curved dural plane that projects inferomedially between the median crest of the


#### **Table 1.**

*Characterization of the sample according to age and gender of patients and size and location of aneurysms, according to Kristh et al [20].*

#### **Figure 6.**

*3-T MRI in T2-weighted turbo-spin sequence in the coronal plane (anterior to posterior, from "A" to "I", respectively) according to the protocol of the present study, demonstrating the anatomo-radiological markers of the paraclinoid region. Note that the optic strut (OS) is identified on MRI as the shade in green and a paraclinoid aneurysm on the right is considered transitional – note in "I", blue arrow, how the most posterior portion of the aneurysm projects into the subarachnoid space. ACP and OS, green; ON, golden; ICA, anterior loop of the internal carotid artery – "C" to "H", red; ICA, cavernous internal carotid artery, horizontal segment – "I"; Aneurysm – "E" to "I", red arrow (adapted and published with permission of Sergio Tadeu Fernandes, MD PhD).*

superior surface of the PDA and the diaphragm sellae [39, 40, 42, 49–51]. The DDR also extends infero-posteriorly between the floor of the optic canal and the posterior part of the roof of the cavernous sinus as illustrated in **Figures 6** and **7**.

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

#### **Figure 7.**

*Removed markers from the previous figure to exercise the identification of structures of interest. Paraclinoid aneurysm on the right is considered transitional – note on "I", blue arrow, how the most posterior portion of the aneurysm projects into the subarachnoid space – aneurysm – "E" to "I", red arrow (adapted and published with permission of Sergio Tadeu Fernandes, MD PhD).*


#### **Table 2.**

*Agreement analysis between MRI and surgery.*

After analysis by the neuroradiologist, the following results were obtained: 11 (44.4%) were classified as intracavernous, 1 (4%) as transitional and 13 (52%) as intradural. Finally, the patients underwent microsurgical treatment of AI clipping. Of the 25 aneurysms analyzed during the microsurgical procedure and exploration of the paraclinoid region, 10 (40%) were classified as intracavernous, 2 (8%) as transitional and 13 (52%) as intradural. The comparative analysis of these data can be seen in **Table 2**.

Data processing showed that the accuracy of magnetic resonance imaging in terms of the intracavernous or intradural location of the aneurysm, with the intraoperative finding as the gold standard and the characteristic "presence of disease" or "positive test" for non-cavernous aneurysm, found sensitivity of 86.7% (95% CI, 59.5–98.3), specificity of 90.0 (95% CI, 55.5–99.8), positive and negative likelihood ratios of 8.7 (CI 95%, 1.3–56.2) and 0.15 (95% CI, 0.04–0.6), respectively, and positive and negative predictive values of 92.9 (95% CI, 66.1–99.8) and 81.8 (95% CI, 48.2–97.7), respectively. The inter-observer agreement by Cohen's Kappa method was almost

perfect (κ = 0.901; p < 0.001; 95% CI, 0.71–1.00) between MRI and surgical procedure findings. The diagnostic test in individuals with no history of SAH had a sensitivity of 92.3% and specificity of 100%. In this circumstance, the 100% specificity demonstrates the superiority of MRI when the aneurysm is intracavernous, that is, it is a method free of false negatives and can be considered the gold standard in ruling out the presence of disease (transitional or intradural aneurysm).

Transferring the issue to daily practice, it can be stated that, when considering the preoperative MRI result in the decision-making process for conservative treatment of paraclinoid aneurysms with no history of SAH, it is likely that all aneurysms considered cavernous, fact they are. The practical significance of these findings is that absolutely all patients eligible for preventive treatment of SAH (transitional or intradural aneurysms) will be so diagnosed and, eventually, only 1 in 10 of treated cases would not need treatment (cavernous aneurysms – false negatives).
