Cranio-spinal Neurosurgical Approaches: Qualitative and Quantitative Analysis and Validation of New Minimally Invasive Methods on Cadaveric Anatomical Models.
Conditions: Minimally Invasive Techniques, Neurosurgical Procedures, Cadaveric Training
Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

 
 
 
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OFFICIAL TITLE OF THE STUDY 
Cranio-spinal Neurosurgical Approaches: Qualitative and Quantitative Analysis and Validation of 
New Minimally Invasive Techniques on Cadaveric Anatomical Models 
NCT NUMBER: 
Not yet assigned 
DOCUMENT DATE: 
16 April 2025 
 
 

 
 
 
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TITLE 
Cranio-spinal Neurosurgical Approaches: Qualitative and Quantitative Analysis and Validation of 
New 
Minimally 
Invasive 
Techniques 
on 
Cadaveric 
Anatomical 
Models. 
 
Acronym: Neuro_SURGEM (Neurosurgical Simulation and Quantitative Evaluation Methods)   
Promoter: 
Fondazione 
Policlinico 
Universitario 
Agostino 
Gemelli, 
Rome, 
Italy 
Date: 16/04/2025 
 
 

 
 
 
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ABSTRACT 
In recent years, the preclinical phase has become crucial for surgical research, as highlighted in the 
IDEAL framework (Idea, Development, Exploration, Assessment, Long-term study), which 
underscores the need for rigorous evaluation in the development of new surgical techniques (1-3). 
Our research focuses on the systematic analysis of different cranio-spinal surgical approaches, using 
an innovative quantification system (BrainChop software). This preclinical study is conducted at the 
"SURGEM" anatomical laboratory at the Catholic University of the Sacred Heart in Rome. 
The study spans 36 months and includes several stages of cadaveric dissection with the aim of 
obtaining: 
1. Quantification methods of working volumes and exposed area; 
2. Analysis of anatomical variants; 
3. Anatomical simulations; 
4. Validation 
of 
new 
instruments/techniques. 
The goal of this study is to deepen, through laboratory simulations, cranial (craniotomy, macro 
and minimally invasive) and spinal approaches with particular emphasis on the quantification 
of working volume and exposed area, anatomical variant analysis, and validation of new 
techniques/instruments (14-24). Using anatomical specimens and a neuronavigation system, 
various surgical techniques will be simulated with different types of dedicated instruments. 
This study will also analyze vascular, nerve, and bone anatomical variants that may influence 
surgical outcomes and intraoperative management of anatomical anomalies. Tumor resections 
will be simulated, with the goal of analyzing in detail the surgical access trajectories and 
resection 
areas. 
35 Anatomical specimens will be used, including the voluntary donation program of the 
Agostino Gemelli University Hospital IRCCS - Catholic University of the Sacred Heart, in 
compliance with Italian law. Dissections will be performed using neurosurgical instruments, 
and 
data 
will 
be 
cataloged 
and 
anonymized, 
with 
proper 
storage.  
This research aims to improve the understanding and effectiveness of cranio-spinal surgical 
approaches, promoting continuous innovation in surgical techniques. At the end of the three-
year project, we expect not only to provide a detailed and quantitative analysis but also to 
make a significant contribution to the scientific literature in surgery and neurosurgery. 
 
INTRODUCTION 
BACKGROUND 
In recent years, the preclinical phase of research in surgery has been recognized as a critical moment 
for the development of new techniques and surgical approaches. The IDEAL framework (Idea, 
Development, Exploration, Assessment, Long-term study) represents a reference model for 
describing the various phases of surgical research, highlighting the importance of preclinical 
evaluation both in the development and validation of new surgical approaches (1–3). 

 
 
 
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In Italy, the Law Number. 10 of February 10, 2020, introduced specific regulations concerning the 
donation of one's body and tissues post-mortem for study, training, and scientific research purposes, 
limited to those who have given their consent during their lifetime. The use of the human body or 
post-mortem tissues is governed by the principles of solidarity and proportionality, and regulated in 
a way that ensures respect for the dignity of the human body. This law has enabled the Fondazione 
Policlinico Universitario Agostino Gemelli  to expand its study, training, and research activities, 
including the possibility of accepting body and tissue donations from individuals who have consented 
during their lifetime, thus contributing to the advancement of medicine and biotechnology. 
The anatomical laboratory provides a controlled environment, ideal for simulating surgical 
procedures, allowing the analysis of multiple variables that influence the effectiveness of the 
procedure and cannot be controlled in clinical practice (4–14). Recently, the Principal Investigator 
(PI) developed, in collaboration with the University of Toronto, a navigation system that allows for 
the quantification of the workspace to define a specific surgical approach (14–19). This new method 
has been used in several anatomy laboratories, including those at the Universities of Brescia, Toronto, 
and Geneva, to conduct comparative quantitative studies on various neurosurgical, otolaryngological, 
and skull base surgery approaches. Some of the results obtained have been published in international 
scientific journals (14–24). 
Objective 
The main objective of this study is to conduct a preclinical and systematic analysis of the various 
cranial and spinal surgical approaches to evaluate their potential and limitations in an objective 
manner. Attention will be particularly focused on the study of skull base approaches, spinal 
approaches, quantitative studies, exploration of anatomical variations, and the validation of new 
surgical approaches and related instruments. 
Endpoints 
Primary Endpoints: 
1. Quantification of Work Volume and Exposed Area in Cranio-Spinal Surgical Approaches 
Work volume represents the three-dimensional operative space created by each cranio-spinal surgical 
approach. Quantification will be performed using BrainChop imaging software on standardized CT 
scans. Segmentation will follow predefined protocols to ensure reproducibility. Higher values indicate 
a larger and more accessible operative corridor. Exposed area corresponds to the two-dimensional 
anatomical surface revealed by each surgical approach. Measurements will be obtained from CT-
based reconstructions using the same standardized segmentation workflow. Higher surface values 
reflect wider surgical exposure. 
Unit of Measure: cubic millimeters (mm³) and square millimeter. 

 
 
 
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Time Frame: Measurements will be obtained twice with BrainChop software for each approach on 
every specimen: before the dissection using baseline CT imaging and after completing the approach 
using repeat CT imaging on the same day. 
Secondary Endpoints: 
1. Analysis of anatomical variations influencing surgical approaches. 
2. Validation of new surgical instruments and techniques on cadaveric specimens. 
3. Average operative time for each surgical approach: Determining the average time required to 
complete each type of surgery (macrosurgical, microsurgical) based on the adopted surgical 
approach. The analysis will focus on the duration of the intervention for each approach, 
comparing the relative efficiency of the techniques. 
4. Assessment of the perceived difficulty by surgeons during the execution of surgical 
approaches: Collecting subjective evaluations on the difficulty of the procedure using a 
difficulty rating scale (e.g., Likert scale), considering factors such as familiarity with the 
technique, the anatomical complexity of the cadaver, and the ergonomics of the instruments 
used. 
5. Assessment of the visibility of target anatomical structures through different visualization 
methods: Measuring the visibility of areas of anatomical interest using different visualization 
methods (macrosurgical, microsurgical). This endpoint will focus on the effectiveness of the 
different modes in providing clear visibility of critical anatomical structures during the 
surgical procedure. 
6. Acceptability and feedback from surgeons on the use of new surgical techniques and 
instruments: Gathering feedback from participating surgeons on the new instruments and 
surgical techniques, evaluating their experience in terms of comfort, ergonomics, ease of use, 
and ease of learning the techniques employed during the simulation. 
7. Effectiveness of dissection and surgical training courses: Measuring the effectiveness of 
dissection and hands-on training courses using cadaveric specimens, through pre- and post-
training tests. This endpoint will focus on the improvement of participants’ technical skills, 
with particular attention to their ability to apply the new surgical techniques learned during 
the simulations. 
Methodology 
Study Design 
This study is a monocentric, observational, non-profit study that will be conducted on cadaveric 
anatomical specimens. No drugs or medical devices will be used on human subjects. The study will 
have a duration of 36 months and will begin after approval from the ethics committee. 
The study will be divided into three distinct phases: 

 
 
 
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• 
First and Second Year: The main objective will be the quantitative analysis of the different 
surgical approaches. This will be accomplished using the innovative research method already 
applied by the Principal Investigator (PI) for the preclinical study of skull base surgical 
approaches. 
• 
Third Year: The focus will be on macroscopically and microscopically visualized skull base 
and spinal approaches. Quantitative analyses will be conducted, relevant anatomical variations 
will be explored, and new surgical approaches and related instruments will be validated. 
 
Setting 
The anatomical dissections will be performed at the SURGEM Laboratory (located in the Settorian 
Room of the Institute of Pathological Anatomy at the Catholic University of the Sacred Heart in 
Rome). Recruitment of specimens began on 15/10/2025 and will continue throughout the study, which 
is expected to last for three years. The dissections, data collection, and analysis will be carried out 
continuously during this period. 
Procedure 
The anatomical specimens will be sourced from the Catholic University of the Sacred Heart's 
voluntary donation program and the Science Care Program. Sixty percent of the specimens will 
undergo specific preparations, including arterial and/or venous injections with silicone, consisting of 
a base and catalyst (Xiameter®, Midland, MI, USA) and colored with Pintasol® (Mixol® Red E-
L3mix, Kirchheim unter Teck, Germany). The specimens will undergo high-resolution CT scans, and 
the DICOM images will be imported into a dedicated neuronavigation system (GTx-Eyes II Approach 
Viewer, University Health Network, University of Toronto, Toronto, Ontario, Canada). In some 
cases, CT scans will be repeated after dissection, and new calculations will be made using the 
neuronavigation software. 
CT scans will be performed at the Institute of Forensic Medicine at the Catholic University of the 
Sacred Heart. The source of the specimens will be tracked and recorded, including: 
• 
Voluntary donation program at the Catholic University of the Sacred Heart, Rome, Italy, in 
accordance with Italian law (LAW 10 February 2020, No. 10 and DECREE OF THE 
PRESIDENT OF THE REPUBLIC 10 February 2023, No. 47); 
• 
Science Care, USA. 
The dissections will be performed using neuro-surgical instruments specific for skull base surgery 
available at the SURGEM laboratory: 
• 
Complete set of Rhoton dissectors (Rhoton Micro Dissector). 
• 
Complete set for skull base surgery (Karl Storz®, Germany). 

 
 
 
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• 
Zeiss microscope (UCSC 119473). 
The specimens will be cataloged according to their source, and anonymized data provided by the 
donor centers will be entered into a database. Proper storage of the specimens will take place at the 
Institute of Pathological Anatomy (Head: Dr. Vincenzo Arena) at the Catholic University of the 
Sacred Heart. Non-fixed specimens will be stored frozen at -20°C in dedicated freezers, while fixed 
specimens (with formalin) will be stored at 4°C in a solution (formaldehyde, glycerol, alcohol reagent, 
and water). 
Variables 
The approaches will be performed in a modular manner, from the least invasive to the most extensive. 
Various surgical approaches will be simulated using surgical instruments dedicated to skull base 
surgery, spinal surgery, and in both macrosurgical and microsurgical visualization modes. 
The quantification of the working volume and the exposed area for each surgical approach will be 
calculated with an open-source software (BrainChop) on the CT scans of the specimens obtained 
before and after surgical dissection. For each specimen's CT scan, the area of interest exposed by the 
different approaches to be compared will be outlined using the BrainChop software (14-24). 
 
Error and Control 
To minimize potential sources of error, rigorous control methodologies will be implemented during 
data collection. Each analysis will be repeated multiple times to ensure the accuracy of the results. 
Sample Definition 
Given the descriptive nature of the study, a formal sample size determination is not required. 
However, we estimate that 35 cadavers will be enrolled over the three-year period. 
Statistical Analysis 
Quantitative variables will be summarized as means and standard deviations, while qualitative 
variables will be reported as absolute and relative frequencies (percentages). The effectiveness of the 
training will be evaluated by testing the mean difference of scores obtained in tests administered 
before and after the training, using the paired Student’s t-test or the Wilcoxon test. 
The difference in execution times between different techniques will be tested using ANOVA or the 
Kruskal-Wallis test. Linear models with random intercepts will be used to compare surgical volumes 
and exposed areas. A 95% confidence interval will be estimated using the bootstrap resampling 
method. 

 
 
 
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Results with p<0.05 will be considered statistically significant. Statistical analysis will be performed 
using STATA software (StataCorp® LLC, College Station, TX, USA). 
Ethical Issues and Informed Consent 
The study will be conducted in accordance with the protocol. No new informed consent will be 
required from the donor's family, as each donor has already provided written informed consent for 
the use of their body in medical research prior to death. Regarding donors, the Institute of Pathological 
Anatomy provides adequate counseling to the families, informing them about the use of the body and 
the studies to be conducted. 
 
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