1. Research protocol The surgical AR neuroendoscopic system in this study mainly
includes three core links:
- (1) virtual image or environmental modeling.
AR systems
use data derived from color or texture differences between anatomical structures in
CT or MRI tomography, as well as whole-brain angiography, to complete a 3D
reconstruction of a subsurface target in a computer. This process can also be done
manually using the 3D-Slicer software.
- (2) Registration of virtual environment and
real space.
Registration technology is essential for AR systems, as it enables
real-time tracking of anatomical structures in the endoscopic field of view.
Registration can be done by a variety of means, such as the 3D Cartesian system,
which is based on framing technology, which can determine the position and attitude
of the imaging device, while also allowing the virtual environment to make rapid
changes and register when the position changes in the real world. Or use frameless
registration to register virtual match points with known anatomical landmarks in
real space.
- (3) The final demand is to combine the virtual environment with the real
environment to display technology.
It can be divided into head-mounted display
(HMD), enhanced external display, enhanced optical system, enhanced window display
and image projection. Using HMDs to overlay virtual environments with video feeds
from real environments (video perspective). Utilize a simple, stand-alone screen as
an enhanced display to display virtual content on a video originating from a
neuroendoscope.
After the above links are successfully achieved, transnasal skull base surgery is
performed using neuroendoscope with AR to achieve real-time tracking, accurately identify
anatomical structures, and reduce the risk of neurovascular injury and complications in
skull base surgery.
Subjects: About 100 cases of neuroendoscopic skull base surgery performed in the
Department of Neurosurgery of the First Affiliated Hospital of Xiamen University,
regardless of gender and age.
Inclusion Criteria: 1. Patients undergoing transnasal endoscopic skull base surgery in
our department. 2. Thin-slice head MRI and CTA scans were performed before surgery.
Exclusion Criteria: 1. Patients without clear preoperative imaging data. 2. Patients who
do not agree to receive AR fusion neuroendoscopic assistance. 3. Patients with incomplete
medical records.
Intervention: Participants were divided into two groups to undergo transnasal skull base
surgery using common neuroendoscopy and neuroendoscopy infused with augmented reality
technology and compared.
Evaluation methods: The surgical effect was evaluated according to the patient's tumor
size, pathological type, operation time, length of hospital stay, complications, and
whether there was a history of pituitary surgery.
Effectiveness evaluation indicators (primary efficacy index and secondary efficacy
index):
The main efficacy indicators: duration of surgery, whether the augmented reality
navigation was successfully established during the operation, whether the augmented
reality navigation was accurate during the operation, the incidence of cerebrospinal
fluid leakage during the operation, and the incidence of damage to important anatomical
structures during the operation Secondary efficacy measures: endocrine improvement rate,
visual field improvement rate, length of hospital stay, etc.
Statistical methods: Chi-square test was used for counting data, t-test was used for
measurement data, and SPSS software was used for data processing.
Participant participation time: one year after the patient is admitted to the hospital to
be discharged.
Location: The First Affiliated Hospital of Xiamen University Hypothesis: Neuroendoscopy
integrated with augmented reality technology can greatly promote intraoperative
orientation and facilitate the surgeon's observation of correlation anatomy. Therefore,
we hypothesize that neuroendoscopy with augmented reality technology can reduce surgical
complications and improve surgical efficacy compared with traditional endoscopy.
All eligible subjects were randomly divided into two groups to undergo traditional nasal
endoscopic surgery and endoscopic transnasal surgery with augmented reality technology,
and relevant data were collected for statistical analysis after the surgery. None of the
subjects were grouped before surgery. Traditional transnasal endoscopic surgery was used
as the control group to evaluate the therapeutic effect of augmented reality endoscopy.
Before the study was carried out, the research group had a comprehensive grasp of the
factors such as the size of the cases requiring nasal surgery and the age and gender
composition of the patients who needed to undergo nasal surgery in our hospital,
established a good sampling framework, and strictly implemented stratified and
proportional sampling, so as to avoid and reduce selective bias. The research team has
done a good job of coordination and mobilization before the investigation, obtained the
cooperation of the department and the relevant departments of the outpatient department,
established a trust relationship with the patients, reduced the refusal of visits,
thereby reducing the selectivity bias, and can improve the authenticity of the interviews
and reduce the bias of information. Avoid and reduce refusals as much as possible. This
study followed ethical principles throughout the process, obtained the trust and
cooperation of patients, and avoided and reduced information bias. Responsible and
communicative team members were selected as investigators to reduce information bias.
The duration of this study was from the time the patient was admitted to the hospital and
the patient was discharged 1 month later, with an average of about 1 month. The follow-up
time was 1 month, 3 months, 6 months and 1 year after surgery, respectively.
The main intervention method in this study was to use a neuroendoscope developed by the
research group integrating augmented reality technology instead of traditional
neuroendoscopy for transnasal skull base surgery.
Study endpoint: The study endpoint is reached if the study subject completes all phases
of the study and follow-up according to the study protocol or withdraws the informed
consent.
Sample size: A total of 100 cases of AR fusion neuroendoscopic transnasal skull base
lesion surgery were completed in 3 years. The expected loss-to-follow/drop-out rate is
less than 5%.
Study intervention: Transnasal skull base surgery using an augmented reality
neuroendoscope developed by the research group instead of a traditional endoscope, which
utilizes the hospital's existing Medtronic S7 navigation and Carl STORZ endoscope, and
the safety of the above devices has been validated. The surgical instruments used to
complete all cases are the same model of the same brand and the same operator, so as to
avoid affecting the surgical process due to hardware reasons and manual operation. For
each completed operation, the patient's relevant imaging information will be backed up,
and the patient's case number will be recorded to prevent the loss of case information.
The registration of intraoperative endoscope and AR was in accordance with the operating
procedures, and after the registration was completed, the body surface markers were used
to ensure the authenticity and accuracy of intraoperative AR images. At the time of
discharge, all cases were informed of regular outpatient re-examination and postoperative
follow-up. The case data is summarized once a month, and a special person is responsible
for keeping the summary. The research team is cooperating and has rich experience in
surgery. We have a professional operating room team to ensure the smooth progress of the
operation. AR navigation may cause errors during the registration process, which should
be operated in strict accordance with the navigation operation procedure, and in vitro
navigation tests using body surface landmarks to reduce errors before performing surgery,
and iCT registration should be used if necessary. In all cases, 4 CT scans of the head, 2
CT scans of the chest, 3 sMRI scans of the brain, 4 blood draws, and 1 bedside
electrocardiogram were planned. If necessary, routine preoperative examinations such as
color ultrasound and Holter electrocardiogram are performed. All surgical instruments are
sterilized and packaged by the Supply Room of the First Affiliated Hospital of Xiamen
University. All surgical equipment All of them are stored in a cool and dry place in the
operating room of the First Affiliated Hospital of Xiamen University, and are adjusted
and regularly maintained by professional engineers. The use of neuroendoscopy,
neuronavigation and other devices is in accordance with the instructions and guidelines.
Measures to reduce bias: data and data collection should be as precise and precise as
possible, and appropriate statistical methods should be selected.
Follow-up and compliance: A total of 4 follow-up visits were performed at 1 month, 3
months, 6 months and 1 year after surgery. During the follow-up, CT/MRI of the head was
taken, blood tests were taken, and endocrine functions such as thyroid and pituitary
gland were checked. By establishing a relationship of trust with patients in advance,
improving service attitude, optimizing the treatment process, strengthening preoperative
and postoperative guidance, and reminding patients to review in a timely manner, patients
can improve their compliance.
Study Intervention Commitment:
Using the existing Medtronic S7 navigation and Carl STORZ endoscope to develop AR
technology, the use of all equipment follows the instructions and guidelines, and the
whole process of the operation is videotaped, and the postoperative review is carried out
by a special person to ensure the smooth implementation of the surgical process, all the
doctor's orders and medications during the patient's stay in the hospital are supervised
by a special person, and the influence of medical drugs and operations on the surgical
results is excluded. Medical records and other medical documents are kept by the research
team, and the patient review reminder and follow-up are carried out by the special
person.
Suspension of study intervention: If a large number of the following serious adverse
reactions occur during the course of the study, the trial will be discontinued after the
comprehensive decision of the investigator.
- (1) Severe cerebrospinal fluid rhinorrhea
complications (2) Symptoms of periorbital bruising and hematoma in the eye, or severe
vision loss, blurred vision and other manifestations.
- (3) Severe nasal bleeding, causing
anemia or even shock, or nasal adhesions, which seriously affects nasal ventilation and
sinus drainage.
- (4) Damage to large blood vessels and nerves, (5) Severe symptoms of
endocrine disorders, (6) Severe cerebral edema or intracranial infection During the study
interruption: carefully check the software and hardware problems of the endoscopy system,
check the accuracy of the image output, and test the effectiveness of the software.
Check
whether there are any problems with the surgical conditions, surgical instruments and
surgical team. and provide effective medical assistance to subjects who have adverse
events. The relevant information of all subjects with adverse events was collected,
including but not limited to: age, gender, time of consultation, image number, diagnosis,
visual field, endocrine status, operation time, whether there was cavernous sinus
hemorrhage during the operation, whether the tumor was completely resected, whether there
was cerebrospinal fluid leakage, whether the augmented reality navigation was
successfully established during the operation, whether the augmented reality navigation
was accurate during the operation, the length of hospital stay, the postoperative visual
field, and the endocrine situation.
Withdraw/Withdraw from the Study Subject: The investigator may suspend or withdraw the
study subject if the study subject has:
- (1) pregnancy (2) significant non-compliance with
the study intervention (3) if there are clinical side effects, abnormal laboratory tests,
or other clinical conditions that make continued participation in the study no longer in
the best interest of the study subject (4) disease progression that necessitates
discontinuation of the study intervention (5) the study subject meets the exclusion
criteria (new or confirmed) (6) the study subject cannot receive the study intervention
for a certain period of time (7) the study subject who signs the informed consent form,
is randomized, but does not receive the study intervention will be replaced.
Study
subjects who have signed informed consent, randomized, received study intervention, and
subsequently withdrawn will be or will not be replaced.
Loss to follow-up: The follow-up period for this study is 1 year from the date of
discharge of the patient, and can be considered lost to follow-up when the study subject
stops the scheduled study follow-up, cannot complete the study-specified procedures, or
the investigator cannot contact the study subject. The loss rate was reduced by recording
a variety of contact information such as telephone number and email address during
subject registration, arranging a special person in the research group to be responsible
for reminding subjects to review and follow-up regularly, designing a stable population
to facilitate follow-up, increasing sample size, and reducing the impact of loss to
follow-up.
Observation items and testing time points: During the subject screening period, ensure
that each subject has an indication for surgery, and there are no contraindications to
surgery. Random sampling, stratified sampling, and confidentiality of the results were
kept to the subjects when grouping. During the intervention period, various examination
indicators and imaging data were collected for the subjects before surgery, 3D modeling
was used for preoperative planning, the accuracy of the 3D model was verified during the
operation, and the surgical operation was performed with augmented reality endoscopy, and
the examination results were collected after surgery to evaluate the surgical effect.
During the follow-up period, telephone follow-up or face-to-face consultations were
conducted at one month, three months, six months and one year after surgery to further
evaluate the efficacy of surgery. Finally, the medical record data were summarized, and
the efficacy of the augmented reality neuroendoscope developed by the research group was
evaluated after statistical analysis.
Efficacy Evaluation Criteria:
1. Evaluation of surgical efficacy:
Effectiveness evaluation indicators: including but not limited to age, gender, time
of consultation, image number, diagnosis, operation time, whether the tumor is
completely resected, whether the augmented reality navigation is successfully
established during the operation, whether the augmented reality navigation is
accurate during the operation, and the length of hospitalization.
Safety evaluation: preoperative visual field, endocrine condition, intraoperative
cavernous sinus hemorrhage, cerebrospinal fluid leakage, postoperative visual field,
endocrine condition, etc.
2. Comprehensive efficacy evaluation: postoperative patient satisfaction, operator
satisfaction, etc.
Observation of adverse events: Adverse events refer to a series of malignant events that
may occur in patients during neuroendoscopic surgery, including but not limited to
endoscopic burns, endoscopic mechanical injury, contamination caused by endoscope
detachment, intraoperative neurovascular injury, intraoperative awakening and awareness,
postoperative cerebrospinal fluid leakage, postoperative nursing negligence, etc.
Monitoring of adverse events: mainly through manual monitoring, manual and electronic
composite monitoring, and automatic monitoring system. The recording, handling and
reporting of adverse events should follow the following principles: 1. Establish an
adverse event reporting system. 2. Respond in time to reduce losses. 3. Treat fairly,
focusing on the system rather than the individual. 4. Establish a mechanism for
discussing errors. 5. Analyze feedback, share information, and enhance collaboration
among researchers 6. Follow up and implement, strengthen management, and strengthen
quality control of the research process 7. Continuous improvement, prevent recurrence,
and continuously optimize the research process.
Quality control and quality assurance of the study: 1. The surgical instruments used to
complete the operation in all cases are the same model of the same brand, and the surgeon
is the same person, so as to avoid affecting the surgical process due to hardware reasons
and human operation. 2. For each completed operation, the patient's relevant imaging
information will be backed up, and the patient's case number will be recorded to prevent
the loss of case information. 3. The registration of the intraoperative endoscope and AR
is in accordance with the operating procedures, and the body surface markers are used for
examination after the registration is completed to ensure that the intraoperative AR
images are true and accurate. 4. Inform all cases of regular outpatient review at the
time of discharge, and maintain postoperative follow-up. 5. Summarize the case data once
a month, and a special person is responsible for keeping the summary. 6. The department
has a large number of surgeries, and there are a variety of cases for study.
Pre-assessment of project risk and risk disposal plan: All surgeries will be performed by
professionals such as surgeons, with tacit cooperation with the research team, rich
surgical experience, and a professional operating room team to ensure the smooth progress
of the operation. Theoretically does not increase any risk to the subject. However, in
the course of routine clinical diagnosis and treatment, once there is any discomfort, the
professional doctors in the research group will give reasonable further treatment to the
subjects.
The surgical instruments used to complete all cases are the same model of the same brand,
and the surgeons are all the same person, so as to avoid affecting the surgical process
due to hardware reasons and human operation.
For each completed operation, the patient-related imaging information will be backed up,
and the patient's case number will be recorded to prevent the loss of case information.
The registration of intraoperative endoscope and AR was in accordance with the operating
procedures, and after the registration was completed, the body surface markers were used
to ensure the authenticity and accuracy of intraoperative AR images.
At the time of discharge, all cases were informed of regular outpatient re-examination
and postoperative follow-up. The case data is summarized once a month, and a special
person is responsible for keeping the summary.
Data security monitoring: Clinical research will develop a data security monitoring plan
based on the size of the risk. All adverse events are recorded in detail, properly
handled and tracked until properly resolved or the condition is stable, and the ethics
committee, competent department, Sponsors and drug regulatory authorities report serious
adverse events and unexpected events, etc., the principal investigator regularly conducts
cumulative reviews of all adverse events, and holds investigator meetings to evaluate the
risks and benefits of the study if necessary, double-blind trials can be urgently
unblinded if necessary to ensure the safety and rights of subjects, independent data
monitors will be arranged to monitor the study data for studies with greater than minimum
risk, and independent data security supervision will be established for high-risk studies
The committee monitors the accumulated safety data as well as the efficacy data to make
recommendations on whether or not to proceed with the study.
XIII. Statistical Processing Statistical analysis was performed using SPSS 22.0 software
(SPSS Inc., Chicago, IL). Quantitative data were described as mean and range. Qualitative
data are described by numbers, rates, and ratios. The normality of the data was tested
using the Kolmogorov-Smirnov test. For continuous variables, if the data are normally
distributed, the t-test was used for comparison between the two groups. If the data
distribution is asymmetrical, the Mann-Whitney U test is used. The chi-square test was
used for the analysis of discontinuous variables. The diagnostic performance of the CAC
test was assessed by constructing receiver operating characteristic (ROC) curves and
calculating the area under the curve (AUC). All statistical tests were bilateral, and
significance was set to P < 0.05 and 95% CI.
2. Research Objectives Main objectives: To explore the solution of integrating AR
technology in the interface of neuroendoscopic view, and use this technology to
complete transnasal and skull base surgery, which is difficult to perform endoscopic
surgery alone Secondary objectives: To provide a reference for the development of
new functions of neuroendoscopy.
