US-CNS
Research type
Research Study
Full title
US-CNS: Multiparametric Advanced Ultrasound Imaging of the Central Nervous System Intraoperatively and Through Gaps in the Bone
IRAS ID
275556
Contact name
Sophie Camp
Contact email
Sponsor organisation
Research Governance and Integrity Team (RGIT)
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
US and several clinically established advanced US techniques are increasingly used to guide neurosurgical procedures. However, the limited evidence base for US-guided resection of brain tumours shows there remains great variability in the accuracy of US in detecting residual disease. Advanced US techniques also show promise in improving tumour detection but each have their own specific limitations. We hypothesise that a combination of technique standardisation and multiparametric application of advanced US techniques will result in improved accuracy in detecting and discriminating residual tumour. We also postulate that the potential uses of these advanced techniques beyond guiding surgery are underexplored in the CNS. In comparison, the role of US and advanced US techniques in understanding disease processes, diagnosis and prognosis have been well established in other organ systems such as the liver, kidneys and thyroid. This current work also aims to assess whether these use cases can be mirrored in characterising brain tumours and whether multiparametric US is possible and of benefit beyond the intraoperative setting through existing bone windows.
1.3. Primary study – The role of multiparametric ultrasound in defining brain tumour boundaries, assessing extent of resection and in characterising disease.
There are several advanced US techniques which are available for real-time intraoperative guidance, which are currently variably adopted and applied.17 Contrast enhanced US (CEUS) role in defining the boundaries of tumour and in visualising tumour vessels has been established, and its role in neuro-oncology has been supported by its recent inclusion in the European Federation of the Societies for US in Medicine and Biology guidelines in 2017.13,18 In comparison, the role of other advanced US techniques such as superb microvascular imaging (SMI) in defining tumour boundaries and assessing residual disease are much less well defined.19 Furthermore, to date, there has been very limited exploration of how these different techniques may complement each other in defining tumour boundaries. This multiparametric application of ultrasound is well established in other organs, particularly the liver. For instance, multiparametric US in the liver has been used to stage fibrosis and provide deep characterisation of liver lesions.20 To date, the largest exploration of multiparametric US in neurosurgery has been a recent observational qualitative review paper describing different observed features across different brain tumours.17 The potential cooperative role of multiparametric US in better defining tumour boundaries and accurately discriminating tumour residual therefore warrants further assessment. The accuracy of SMI in delineating tumour boundaries also needs assessment. Extending beyond intraoperative guidance, we postulate that multiparametric US may provide further insight into brain tumour pathology, which, similar to other organ systems, could impact on prognosis and response to therapy.15 This is especially relevant in neuro-oncology surgery where tumours are not removed in one piece but in multiple small pieces where histological analysis is typically limited to small samples, which may not be entirely representative of the whole tumour and are sometimes insufficient for extended pathological examination. Thus we postulate that multiparametric advanced US may be useful for tumour grading and furthering understanding tumour behaviour by providing whole tumour views of vessel architecture, blood supply and tumour stiffness.
Primary hypothesis:
1. Multiparametric US will improve delineation of tumour boundaries and residual tumour detection.
Secondary hypothesis:
1. Multiparametric US may provide further insight into brain tumour pathology and behaviour.
1.4. Sub-Study – Feasibility of multiparametric, extra-operative, brain ultrasound through bone windows.Multiparametric US is used in neonates as a non-invasive, safe tool for visualising the brain, for monitoring of pressure inside the head and for assessing blood supply to the brain.21–25 In neonates, US is performed through natural gaps in the developing skull called fontanelles. In adults, cranial US is greatly limited by the skull which blocks the majority of the US beam. Despite this, it is possible to visualise the brain through either naturally occurring or acquired bone windows that have been made as part of a patient’s surgical care. Only a few small studies have attempted multiparametric US in adult patients with a surgically acquired bone window where part of their skull has been removed (decompressive craniectomy) to alleviate raised pressure inside the head (intracranial pressure, ICP).26–30 These studies have demonstrated a possible role of US in assessing ICP and brain blood supply (cerebral perfusion) in adults post brain surgery.
Acute brain injuries such as from trauma or a stroke result in brain swelling which rapidly increase the pressure inside the head whilst brain tumours as they grow can slowly increase ICP. Raised ICP is one of several factors that can reduce blood supply to the brain which is typically difficult to monitor directly in adults. The ability of US to non-invasively assess ICP and brain blood supply would be of interest in critical care as optimisation of cerebral perfusion, and early detection of impaired perfusion is essential to prevent cerebral damage. Furthermore, these tools may provide insight and understanding into the changes in cerebral perfusion and vascular dynamics that occur post decompressive surgery and in relation to other factors such as blood pressure and oxygenation. Outside of this setting, we postulate that it may also be possible to perform extra-operative US in patients with brain tumours who, as part of their treatment, often have surgically acquired bone windows. If proven feasible, this could have applications as a further method of disease monitoring. Finally we hypothesise that patients who require decompressive craniectomy for acutely raised intracranial pressure will have differences in vessel blood flow and cerebral stiffness when compared to patients with brain tumours. Through exploring the relationship between cerebral perfusion, vascularity and brain stiffness in these two different groups we anticipate a larger multicentre study will follow to look at improving monitoring and management of these patient groups.
Sub-study primary hypothesis:
1. Extra-operative multiparametric US is possible through bone windows such as burr holes and craniectomies.
Sub-study secondary hypothesis:
1. Extra-operative multiparametric US may provide further insight into cerebral perfusion, microvascularity, and brain stiffness in patients post decompressive surgery.
2. Extra-operative multiparametric US may allow monitoring of brain tumours.
3. Cerebral perfusion, microvascularity and brain stiffness will be different between patients with acutely raised intracranial pressure and patients with brain tumours, where the elevated pressure is more gradual.REC name
Wales REC 5
REC reference
22/WA/0259
Date of REC Opinion
26 Oct 2022
REC opinion
Further Information Favourable Opinion