1.1  Introduction: Brain tumors, particularly malignant ones such as gliomas, pose significant challenges in neurosurgery due to their complex locations and proximity to critical vascular structures.1,2 The primary goal in brain tumor surgery is to maximize tumor resection while minimizing damage to surrounding healthy brain tissue and vital blood vessels. However, this balance is difficult to achieve, especially when tumors are located near or involve important venous structures, such as dural venous sinuses or deep cerebral veins.

Injury to these venous structures during surgery can result in catastrophic outcomes, including venous infarction, hemorrhage, and brain swelling, which significantly worsen the patient’s prognosis and quality of life. Despite advancements in surgical techniques and technologies like stereotactic neuro-navigation, the risk of vascular injury remains a significant concern due to factors like brain shift during surgery, which can reduce the accuracy of preoperative imaging.

 

Microvascular Doppler (MVD) is a real-time intraoperative tool that has shown promise in identifying and protecting vascular structures during surgery.3 MVD can provide surgeons with crucial information about blood flow and the location of vessels that may not be visible through conventional imaging techniques. This study aims to evaluate the utility of MVD in improving the safety and outcomes of brain tumor surgeries, specifically by preventing injury to critical venous structures.

 

1.2  Brief Description of the Hypothesis: The central hypothesis of this study is that the use of Microvascular Doppler (MVD) during brain tumor resection will significantly reduce the incidence of intraoperative vascular injury, thereby improving surgical outcomes and reducing postoperative complications such as venous infarcts and neurological deficits. The hypothesis is based on the premise that real-time intraoperative guidance provided by MVD will allow for more precise identification and preservation of critical venous structures that are at risk during tumor resection.

 

1.3  Statement of the Problem: Brain tumors, especially those located near essential venous structures, present a unique challenge in neurosurgery. The risk of damaging these structures during tumor resection is high, leading to severe postoperative complications that can significantly affect patient outcomes. Traditional imaging and navigation techniques, while useful, have limitations, particularly in accurately mapping venous structures in real- time due to issues such as brain shift during surgery.

 

Current methods often rely on the surgeon’s experience and the use of intraoperative imaging, which may not always provide sufficient information about the venous architecture. This limitation increases the risk of venous injury, which can lead to life- threatening complications such as intracranial hemorrhage, venous infarction, and severe neurological deficits. Therefore, there is a critical need for a reliable intraoperative tool that can enhance the surgeon’s ability to identify and protect venous structures during brain tumor surgery.

This study addresses this unmet need by investigating the use of Microvascular Doppler, which has the potential to provide real-time feedback on the location and condition of blood vessels during surgery, thus reducing the risk of vascular injury and improving patient outcomes.

1.1     Primary Objective:
·       To evaluate the effectiveness of Microvascular Doppler (MVD) in preventing intraoperative vascular injury during brain tumor resections.

Secondary Objectives:
·       To compare postoperative outcomes between patients undergoing surgery with MVD assistance and those without.

·       To determine the frequency of intraoperative decision changes prompted by MVD findings (e.g., adjustments in surgical approach or extent of resection).

·       To compare the extent of resection of tumors

 

1.2   Expected Outcome
The study is expected to yield several important outcomes that could have a significant impact on the practice of neurosurgery, particularly in the context of brain tumor resection:

a)     Reduction in vascular injury by 98%: The historical data of injury rate in control group is approximately 3%. We expect it to be reduced to 0.01% by using the MVD.

b)    Significant reduction in overall complication rate: The study aims to demonstrate a statistically significant decrease in the overall complication rate in the MVD group compared to the control group.

c)     Improved patient outcomes: This may include faster recovery times, improved functional status, and enhanced quality of life in the MVD group.

d)    Improved tumor resection rates: The MVD group may have significant increased tumor resection rates than the control group.

1.1   Sample Size/Number of Participants: The study will include a total of 198 patients undergoing brain tumor resection. These patients will be randomly divided into two groups: Group A (n=198): Patients who will undergo surgery with the assistance of Microvascular Doppler (MVD).

Group B (n=198): Patients who will undergo surgery without the use of MVD (control group).

 

1.2    Justification for the Sample Size
 

To ensure adequate statistical power for this study, a sample size calculation was performed. Based on the expected control group injury rate of 3% with a 75% indirect complication rate,4 resulting in an

effective complication rate of 2.25%, and the anticipated MVD group injury rate of 0.01% with an assumed 5% indirect complication rate, resulting in an effective complication rate of 0.0005%, the required sample size per group was estimated to be approximately 198 participants. This calculation was based on a desired power of 80% and a significance level of 0.05, using the following formula for comparing two proportions.

1.1    Brief Description of Protocol
a.     Preoperative Assessment:

·      All patients will undergo standard preoperative imaging, including MRI and/or CT angiography, to map the tumor and surrounding vascular structures.

·      Patients will be randomly assigned to either Group A (MVD-assisted surgery) or Group B (standard surgery without MVD).

·      Informed consent will be obtained from all participants.

 

b. Surgical Procedure:
 

Group A: Surgeons will use the Microvascular Doppler during tumor resection. The MVD probe will be applied intermittently throughout the procedure to identify and monitor critical venous structures in real-time. This feedback will guide the surgeon in navigating around these structures, adjusting the surgical approach as necessary.

 

Group B: Surgeons will rely on standard neuro-navigation and imaging techniques without the use of MVD. The procedure will follow the conventional approach, with careful attention to the preoperative imaging maps.

 

c.  Intraoperative Monitoring:
In both groups, the extent of tumor resection and any venous structures at risk or injured will be documented in detail. The surgical team will note any instances where the MVD influenced a change in the surgical plan (for Group A).

d. Postoperative Assessment:
·      Postoperative MRI or CT scans will be performed within 48 hours to assess the extent of resection, any residual tumor, and potential venous injury or infarction.

·      Patients will be monitored for immediate postoperative complications, including neurological deficits and venous infarcts.

·      Follow-up will occur at 1 month, 3 months, and 6 months post-surgery, focusing on neurological function, and recovery

e.  Data Collection and Analysis:
·      Data will be collected on the incidence of intraoperative venous injury, extent of tumor resection, postoperative complications, and recovery outcomes.

·      Statistical analysis will compare the primary and secondary outcomes between Group A and Group B using appropriate methods (e.g., chi-square test, t-test, or ANOVA).

 

1.2           Inclusion and Exclusion Criteria Inclusion Criteria:
a.     All patients diagnosed with a brain tumor that requires surgical resection.

b.     Patients who provide informed consent to participate in the study.

 

Exclusion Criteria:
Patients with severe comorbidities that may significantly impact surgical risk or postoperative recovery.

 

 

2.     Workplan & Timeline:
A.  Preparation Phase (Weeks 1-6)

·       Ethics approval, consent forms, acquiring microvascular doppler

B.               Patient Recruitment, Preoperative assessment, Surgeries, postoperative assessment (Weeks 7- 130)

·       Begin patient recruitment and preoperative assessments, including imaging and randomization into Group A (MVD) and Group B (control).

·       Surgeries to be performed

·       Continue recruitment, ensuring a balanced and representative sample across both groups.

 

C.  Postoperative Monitoring and Follow-Up (Weeks 131-136)

·       Perform immediate postoperative assessments, including MRI or CT scans, and document early postoperative outcomes.

·       Conduct 1-month and 3-month follow-up assessments, focusing on neurological function and recovery.

D.  Data Analysis and Reporting (Weeks 137-138)

·       Analyze the collected data, comparing the outcomes between Group A and Group B.

·       Draft the study findings, including statistical analysis, interpretation, and conclusions.

·       Review and revise the study report, incorporating feedback from collaborators.

·       Finalize the report and prepare for publication or presentation.

1.     Is there an external laboratory/outsourcing involved in investigations?
(Select any one from following)

o No

 

2.     References: (Please use font size 10 for referencing)

1.   Alafandi A, Tbalvandany SS, Arzanforoosh F, et al. Probing the glioma microvasculature: a case series of the comparison between perfusion MRI and intraoperative high-frame-rate ultrafast Doppler ultrasound. Eur Radiol Exp. 2024;8(1):13. doi:10.1186/s41747-023-00406-0

 

2.   Courtin C, Lacoin G, Remenieras JP, et al. Tumoral and peritumoral vascularization of brain tumours: a study comparing an intraoperative ultrasensitive Doppler and a preoperative first-pass perfusion MRI. Neurochirurgie. 2023;69(6):101493. doi:10.1016/j.neuchi.2023.101493

 

3.   Liang B, Feng D, Lyon KA, Zhang Y, Huang JH. Intraoperative utilization of Microvascular Doppler for the detection of intracranial venous structures during tumor resection - A technical note. J Clin Neurosci. 2021;88:10-15. doi:10.1016/j.jocn.2021.03.023

 

4.   Courtin C, Lacoin G, Remenieras JP, Rousselot CD, Dujardin PA, Zemmoura I, Cottier JP. Tumoral and peritumoral vascularization of brain tumours: a study comparing an intraoperative ultrasensitive Doppler and a preoperative first- pass perfusion MRI. Neurochirurgie. 2023 Nov 1;69(6):101493.