Improving Ultrasound Images in Brain Tumour Surgery With the Use of an Acoustic Coupling Fluid Mimicking Brain Tissue.

Study Overview
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Brief Summary
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Tools for improving brain tumor surgery, in particular for gliomas, are increasing. There seems to be an agreement that achieving extensive resections, when done safely without jeopardizing neurological function, improves survival. Ultrasound is currently used as a tool for providing 2D or 3D images for tumor localization and resection control. For the use in resection control the resection cavity is filled with saline to provide acoustic coupling between the ultrasound transducer and tissue. However, attenuation of acoustic waves is very low in saline compared to the brain and this difference in attenuation is the cause of artifacts that may severely degrade the ultrasound images. Such artifacts are seen as high-intensity signal at the resection cavity wall and beyond. The artificial signal enhancement can potentially mask small tumor remnants and is generally making the interpretation of images more difficult. This research group has developed an acoustic coupling fluid intended for use in the resection cavity instead of saline. Tests in laboratory measurements have shown that the fluid reduces artifacts and has the potential to enhance ultrasound image quality in brain tumor surgery. Three different concentrations of the acoustic coupling fluid have been tested in a phase 1 study that included 15 patients with glioblastoma. The concentration that provided the optimal ultrasound images, from qualitative and quantitative inspection, is used in the current phase II study. This study is a randomized controlled trial aiming to include 82 patients with glial brain tumours. Its purpose is to test the fluid during surgery of glial brain tumours to further investigate safety and efficacy.

Official Title
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Improving Ultrasound Images in Brain Tumour Surgery With the Use of an Acoustic Coupling Fluid Mimicking Brain Tissue: a Phase II Technical and Safety Study

Conditions
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Brain Neoplasms, Glioma

Intervention / Treatment
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* Biological: acoustic coupling fluid
* Biological: Ringer's acetate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A diffuse glial tumour (high-grade (stage 1), low-grade or high-grade (stage 2)) is suspected from the diagnostic magnetic resonance images (MRI). In cases where histopathology is not known from previous biopsy or resection (i.e. diagnosis is suspected based on MRI findings and not from previous surgery) a tissue sample for frozen section is necessary to confirm the diagnosis. Karnofsky performance status >=70 Exclusion Criteria: Not able to consent (e.g. severe cognitive impairment) Intended biopsy only (meaning: cases not suitable for resection) Hypersensitivity to egg protein Hypersensitivity to soya or peanut protein Hypersensitivity to glycerol Pregnancy of breast-feeding Intention to become pregnant during the time of the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High grade gliomas stage 1 ACF<br>In the first stage 12-15 patients with high-grade gliomas will be included in the trial (acoustic coupling fluid) group. | Biological: acoustic coupling fluid<br>* ultrasound images obtained with both ACF and Ringer's acetate<br>* Other names: ACF;|
| Experimental: Low-high grade gliomas stage 2 ACF<br>If the interim safety assessments validate that the study can continue, the second stage involves inclusion in the trial (acoustic coupling fluid) group of 22-25 patients with both low-grade and high-grade glioma | Biological: acoustic coupling fluid<br>* ultrasound images obtained with both ACF and Ringer's acetate<br>* Other names: ACF;|
| Active Comparator: High grade gliomas stage 1 control<br>In the first stage 12-15 patients with high-grade gliomas will be included in the Ringer's acetate (control) group. | Biological: Ringer's acetate<br>* ultrasound images obtained with Ringer's acetate only<br>|
| Active Comparator: Low-high grade gliomas stage 2 control<br>If the interim safety assessments validate that the study can continue, the second stage involves inclusion in the Ringer's acetate (control) group of 22-25 patients with both low-grade and high-grade glioma | Biological: Ringer's acetate<br>* ultrasound images obtained with Ringer's acetate only<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| difference in serious adverse event rates (test minus control) | Non-inferiority (i.e. test serious adverse event rate is not worse than control) is shown if the 95%-confidence interval around the mean difference in event rates has an upper value below 0.3 which is the predefined margin | 72 hours | 
| difference in serious adverse event rates (test minus control) | Non-inferiority (i.e. test serious adverse event rate is not worse than control) is shown if the 95%-confidence interval around the mean difference in event rates has an upper value below 0.3 which is the predefined margin | 30 days | 
| difference in serious adverse event rates (test minus control) | Non-inferiority (i.e. test serious adverse event rate is not worse than control) is shown if the 95%-confidence interval around the mean difference in event rates has an upper value below 0.3 which is the predefined margin | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| image artefacts | during the operation; Qualitative score of ultrasound image quality (poor-medium-good) | 1 day | 
| image artefacts | during the operation; Qualitative score of artefacts in ultrasound images (none-some-much) | 1 day | 
| depiction of outline of the anatomy surrounding the resection cavity | during the operation; Qualitative score of ultrasound image quality (poor-medium-good) | 1 day | 
| depiction of outline of the anatomy surrounding the resection cavity | during the operation; Qualitative score of artefacts in ultrasound images (none-some-much) | 1 day | 
| image signal-to-noise ratio | after the operation: image analysis by quantitative measurements of signal-to-noise ratio (SNR) | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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brain, ultrasonography, ultrasonics, surgery