Quantitative Anatomical Studies in Neurosurgery: A Systematic and Critical Review of Research Methods

Background: The anatomy laboratory can provide the ideal setting for the preclinical phase of neurosurgical research. Our purpose is to comprehensively and critically review the preclinical anatomical quantification methods used in cranial neurosurgery. Methods: A systematic review was conducted following the PRISMA guidelines. The PubMed, Ovid MEDLINE, and Ovid EMBASE databases were searched, yielding 1667 papers. A statistical analysis was performed using R. Results: The included studies were published from 1996 to 2023. The risk of bias assessment indicated high-quality studies. Target exposure was the most studied feature (81.7%), mainly with area quantification (64.9%). The surgical corridor was quantified in 60.9% of studies, more commonly with the quantification of the angle of view (60%). Neuronavigation-based methods benefit from quantifying the surgical pyramid features that define a cranial neurosurgical approach and allowing post-dissection data analyses. Direct measurements might diminish the error that is inherent to navigation methods and are useful to collect a small amount of data. Conclusion: Quantifying neurosurgical approaches in the anatomy laboratory provides an objective assessment of the surgical corridor and target exposure. There is currently limited comparability among quantitative neurosurgical anatomy studies; sharing common research methods will provide comparable data that might also be investigated with artificial intelligence methods.


Introduction
In recent years, evidence-based medicine has gained significant importance in surgery.In this scenario, the IDEAL (Development, Exploration, Assessment, and Long-term study) paradigm was the first promoter of evidence-based surgery [1][2][3][4].IDEAL describes the different phases and challenges of research in surgery and includes a specific phase of preclinical research that can be performed in the anatomy laboratory.Quantitative anatomical research in neurosurgery still poses the following considerable challenges: despite the evolving innovation in surgical technologies (e.g., microscope, endoscopic-assisted techniques, robotics-assisted procedure), objective and shared methods to compare different surgical approaches are often lacking.These seem particularly important in neurosurgery, as even minor differences in surgical technique can significantly affect patient outcomes [5].
Over the last three decades, different quantitative methods have been reported in anatomical neurosurgical research.However, the heterogeneity and multitude of these methods and the different measured parameters complicate the panorama of neurosurgical anatomical quantification.This paper aims to provide a systematic and critical review of the current literature on preclinical anatomical quantification and the comparison of cranial neurosurgical approaches, analyze the proposed research methods and the studied features, and discuss their advantages and disadvantages.

Literature Search
The systematic review was performed per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines [6].Two authors performed a systematically comprehensive literature search of the databases PubMed, Ovid MEDLINE, and Ovid EMBASE.The first literature search was performed on 10 April 2023, and the search was updated on 10 May 2023.A combination of keyword searches was performed to generate a search strategy.The search keywords, including "anatomy", "quantification", "neurosurgery", "approach", "comparison", and "surgery", were used in both AND and OR combinations.Studies were retrieved using the following Medical Subject Heading (MeSH) terms and Boolean operators: ("neurosurgical" OR "neurologic surgery") AND ("approaches" OR "open" OR "microsurgery" OR "endoscopy" OR "endonasal" NOT "transorbital") AND ("anatomy" OR "anatomical studies" OR "preclinical" OR "quantitative" NOT "qualitative") AND ("comparison" OR "quantification" OR "methods" OR "conservative").Other pertinent articles were identified through reference analysis of selected papers.A search filter was set to show only publications over the designated period, 1990-2023.
All studies were selected based on the following inclusion criteria: (1) English language; (2) articles that quantify and compare anatomical features of different neurosurgical approaches in the anatomy laboratory; (3) articles that quantify and compare anatomical features of different neurosurgical approaches in a virtual environment.The following exclusion criteria were employed: (1) studies that qualitatively compare surgical approaches; (2) studies reporting on neurosurgical approaches other than cranial.
The list of identified studies was imported into Endnote X9, and duplicates were removed.Two independent researchers (E.A. and L.D.M.) checked the results according to the inclusion and exclusion criteria.A third reviewer (A.F.) resolved all disagreements.Then, eligible articles were subject to full-text screening.

Data Extraction
For each study, we abstracted the following information: year of publication, quantified feature, quantified parameter, method, tool, and pros and cons of each technique.

Outcomes
Our primary outcomes were measurements related to the surgical corridor and target exposure.As for the surgical corridor, the following parameters were extrapolated from the analyzed studies: volume, surgical freedom or maneuverability, surgical window, and angle of view.Considering the target exposure, the following measurement techniques have been collected: anatomical structures visualization, linear measurements, areas, and volumes.

Risk of Bias Assessment
The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included studies.Quality assessment was performed by assessing the selection criteria, comparability of the study, and outcome assessment.The ideal score was 9. Higher scores indicated better quality of studies.Studies receiving 7 or more points were considered high-quality studies.Two authors performed the quality assessment independently.When discrepancies arose, papers were re-examined by the third author.

Statistical Analysis
Descriptive statistics were reported, including ranges and percentages.All statistical analyses were performed using the R statistical package v3.4.1 (http://www.r-project.org(accessed on 1 July 2023)).

Literature Review
A total of 1667 papers were identified after duplicate removal.After title and abstract analysis, 200 articles were identified for full-text analysis.Eligibility was ascertained for 114 articles.The remaining 86 articles were excluded for the following reasons: (1) studies were not comparative (37 articles), ( 2) studies reporting only on qualitative comparison (39 articles), (3) overview studies (5 articles), ( 4) studies lacking methods details (4 articles), and ( 5) studies reporting on neurosurgical approaches other than cranial (1 article).All studies included in the analysis had at least one or more outcome measures available.Figure 1 shows the flow chart according to the PRISMA statement.
Descriptive statistics were reported, including ranges and p analyses were performed using the R statistical package v3.4.1 ( (accessed on 1 July 2023)).

Literature Review
A total of 1667 papers were identified after duplicate remova analysis, 200 articles were identified for full-text analysis.Eligib 114 articles.The remaining 86 articles were excluded for the follo were not comparative (37 articles), (2) studies reporting only on (39 articles), (3) overview studies (5 articles), (4) studies lacking cles), and ( 5) studies reporting on neurosurgical approaches othe All studies included in the analysis had at least one or more outc Figure 1 shows the flow chart according to the PRISMA statemen

Review Data and Outcomes
A total of 114 articles were included in our systematic review ranged from 1996 to 2023 as follows: four articles were publishe articles were published from 2000 to 2004 (14.9%), 32 articles from from 2010 to 2014 (25.5%), 20 from 2015 to 2019 (17.5%), and 12 (10.5%).Table 1 lists all the articles included in our review ordered     all the articles included in our review ordered per year of publication.The surgical corridor and target were quantified on 69 articles (60.5%) and 94 articles (82.5%), respectively.

Review Data and Outcomes
The quantified parameters of the surgical corridor were the angle of view in 42 articles (60.9%), surgical freedom or maneuverability in 20 (29%), and its volume in 16 (23.2%);the surgical window was quantified in 4 (5.8%)articles.
Tables 2 and 3 summarize the quantified parameters, with respective methods and tools, and the advantages and disadvantages of each reported technique.

Discussion
This systematic literature review has collected and analyzed all the studies published since 1996 reporting the anatomical quantification and comparison of neurosurgical approaches.
With its constant advancements in surgical innovation and technology, neurosurgery requires objective methods to compare various surgical approaches [5,74,126,127].Even minor differences in surgical technique can significantly impact patient outcomes in this field, and personal experience alone is no longer enough for ideal surgical decision-making.As shown by the various studies analyzed, quantifying neurosurgical approaches also aids in interpreting research results and promotes evidence-based medicine.
The systematic review revealed that, even if the first quantitative anatomical studies in neurosurgery were published in 1996, most were published after 2004 and mainly concentrated on target exposure analysis, thanks to the implementation of new technologies and dedicated software applied to preclinical research.It emerged that the quantitative measurements were initially limited to providing partial measurements of the surgical volumes, and the analysis of the surgical corridor has moved toward target exposure with the analysis of the exposure area (Figure 2).It also emerged that the angle of view was the most frequently quantified parameter related to the surgical corridor, with 60% of the articles reporting its measurement.On the contrary, the surgical window was quantified in fewer articles, suggesting the difficulty of replicating this measurement.Regarding target exposure measurements, the exposure area was the most frequently quantified parameter, followed by linear measurements and visualization methods.These findings underscore the significance of assessing the extent of target exposure and the accuracy of surgical maneuvers during different neurosurgical approaches.
The systematic review also included a risk of bias assessment using the Newcastle-Ottawa Scale (NOS).The NOS allowed for evaluating the quality of the included studies based on selection criteria, comparability of the study, and outcome assessment.This assessment ensured that the included studies were reliable and provided robust evidence for quantifying and comparing neurosurgical approaches.
Choosing the proper research method is also paramount in quantitative anatomical studies.Direct measurements might be the best option to collect a relatively small amount of data with limited error, e.g., the length of a nerve exposed from different approaches.Neuronavigation-based methods, developed with dedicated software, allow the straightforward quantification of all the features that define the surgical pyramid, which is specific to each cranial neurosurgical approach.They can provide real-time data acquisition but also have the advantage of post-dissection data analyses, including the definition of the area of interest exposed by a specific approach.
Using standardized measurement techniques, researchers can accurately analyze and compare outcomes across different studies, enhancing the reliability and validity of their findings.This might contribute to accumulating robust evidence to guide clinical decision-making and improve patient outcomes.Furthermore, anatomical quantification facilitates the development of strategic surgical roadmaps, especially for deep-sited regions and complex targets.Additionally, quantifying neurosurgical approaches is essential for promoting new surgical strategies.For example, quantitative anatomical research has been critical in documenting the potential advantages of transnasal endoscopic It also emerged that the angle of view was the most frequently quantified parameter related to the surgical corridor, with 60% of the articles reporting its measurement.On the contrary, the surgical window was quantified in fewer articles, suggesting the difficulty of replicating this measurement.Regarding target exposure measurements, the exposure area was the most frequently quantified parameter, followed by linear measurements and visualization methods.These findings underscore the significance of assessing the extent of target exposure and the accuracy of surgical maneuvers during different neurosurgical approaches.
The systematic review also included a risk of bias assessment using the Newcastle-Ottawa Scale (NOS).The NOS allowed for evaluating the quality of the included studies based on selection criteria, comparability of the study, and outcome assessment.This assessment ensured that the included studies were reliable and provided robust evidence for quantifying and comparing neurosurgical approaches.
Choosing the proper research method is also paramount in quantitative anatomical studies.Direct measurements might be the best option to collect a relatively small amount of data with limited error, e.g., the length of a nerve exposed from different approaches.Neuronavigation-based methods, developed with dedicated software, allow the straightforward quantification of all the features that define the surgical pyramid, which is specific to each cranial neurosurgical approach.They can provide real-time data acquisition but also have the advantage of post-dissection data analyses, including the definition of the area of interest exposed by a specific approach.
Using standardized measurement techniques, researchers can accurately analyze and compare outcomes across different studies, enhancing the reliability and validity of their findings.This might contribute to accumulating robust evidence to guide clinical decision-making and improve patient outcomes.Furthermore, anatomical quantification facilitates the development of strategic surgical roadmaps, especially for deep-sited regions and complex targets.Additionally, quantifying neurosurgical approaches is essential for promoting new surgical strategies.For example, quantitative anatomical research has been critical in documenting the potential advantages of transnasal endoscopic transclival approaches [99,109].
Life 2023, 13, 1822 14 of 21 While anatomical quantitative neurosurgical studies share similar research objectives, they have different research methods and are not comparable.Furthermore, despite incorporating modern technology into the research methodology, there often needs to be more adherence to scientific principles, resulting in a limited broad applicability of the findings.To address these issues, advancements in information technology and use big data analysis techniques through artificial intelligence methods are being increasingly implemented in quantitative neurosurgical anatomy research [128,129].The final goal is to establish an evidence-based approach and achieve greater standardization and reliability in the research process.
Over the years, our research group has published several anatomical quantitative studies [96,[98][99][100]106,107,109,110,113,114,116,127,130], focusing on the quantification of both the surgical volume and the exposure area.In accordance with our experience and with the aim of promoting standardization of the methods of quantification, we detail the minimum instrumentation necessary for an anatomical laboratory that wants to carry out quantitative studies.In detail: (1) Specimens:

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A minimum number of specimens equal to or greater than 5 so that the sample size of the data obtained allows the obtaining of statistically strong results;

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Better alcohol-fixed specimens, as they have a greater preservation of the anatomical tissues and the respect of the relationships between the neurovascular structures, they convert more over time.

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Navigation system composed by a navigation hardware and a dedicated navigation software (e.g., ApproachViewer, part of GTx-UHN-GuidedTherapeutics software developed at University Health Network-Toronto, Canada).
(6) Statistical analysis: • Software for statistical analysis (e.g., R-Studio); • Ideal is the collaboration and support of a biostatistician.

Conclusions
The quantification of neurosurgical approaches can assess target exposure and different surgical corridor parameters, including volume, angle of view, surgical freedom, and surgical window.These measurements can provide valuable insights into the feasibility and effectiveness of a specific approach, helping surgeons decide the best surgical approach for a specific patient.Neuronavigation-based research methods have the advantage of being relatively straightforward in data collection while also providing the possibility of post-dissection analyses.More standardization is needed to collect data that are comparable across different studies.

Figure 1 .
Figure 1.PRISMA flow diagram depicting the literature search process

Figure 2 .
Figure 2. Timeline depicting the evolution of neurosurgical approaches quantification and comparison.

Figure 2 .
Figure 2. Timeline depicting the evolution of neurosurgical approaches quantification and comparison.

•( 3 )
Parameters: gantry of 0 • , scan window diameter of at least 225 mm and pixel size of more than 0.44 × 0.44; • Images recorded in DICOM format.Surgical instruments and tools: • Microscopes; • Endoscope with 0 • and angled optics (at least 30 • and 45 • ); • Straight and curved microscopic and endoscopic instruments.

Table 1 .
List of all the articles included in our systematic review ordered per year of publication.

Table 2 .
Summary of different methods and tools, with corresponding pros and cons, described in the literature for quantifying surgical corridor parameters.

Table 3 .
Summary of different methods and tools, with corresponding pros and cons, described in the literature for quantifying target exposure parameters.