Periodic Reporting for period 1 - HyperProbe (Transforming brain surgery by advancing functional-guided neuronavigational imaging)
Reporting period: 2022-10-01 to 2023-09-30
The HyperProbe project aims at delivering the technological capacity, based on optical imaging, to shape the future of neuronavigation in brain surgery, by centering it on real-time, quantitative monitoring of brain activity and functions, with and without cerebral stimulation, to better assist and guide neurosurgeons.
Measuring brain functional activity is of paramount importance during neurosurgery, such as in glioma and glioblastoma (GBM) removal, due to the critical needs for surgeons to: (1) differentiate healthy tissues from tumor/pathological ones; and (2) preserve the integrity of the cerebral functions of the patients intra- and post-surgery. For this reason, brain activity stimulation plays a fundamental role in current neuronavigation approaches for localizing, identifying and assessing areas of cortical and subcortical functions. Several paradigms of brain stimulation are used intraoperatively, mainly depending on which regions of the cortex are targeted, spanning from cognitive tasks on awaken patients (e.g. for speech and visual functions) to electro-stimulation (e.g. for sensorial and motor functions). The latter can be performed in multiple ways, including direct transcortical and/or subcortical stimulation with probes, as well as indirect stimulation and monitoring of muscular responses via electrodes. However, all these types of simulations present limitations, such as different degrees of invasiveness, lack of real-time, quantitative information, reduced specificity and sensitivity. Furthermore, current imaging techniques used to measure brain activity in neurosurgery, either at resting state or during stimulation, are also affected by similar constraints, either (1) being based on static, pre-surgical assessments (e.g. MRI, PET-CT), or (2) for intraoperative modalities (e.g. fluorescence imaging), providing low spatial resolution, low specificity to cerebral functions and limited breadth of information. Overcoming the above-mentioned limitations in neurosurgical planning and management will require to transform and advance current clinical practice towards a functional-guided neuronavigation approach that is capable of providing assistance to neurosurgeons in decision-making with a real-time, quantitative and accurate assessment of brain activity intraoperatively. Therefore, in this project we will design, develop and validate clinically a novel, all-optical, multifunctional imaging device that can lead such transformation and advancement by providing exhaustive characterization of the morpho-chemical features of cerebral tissue during surgery. Such a device can then allow surgeons to access unprecedented functional, structural and pathological information that can improve patient treatment during a number of neurosurgical practices, such as glioma and GBM resection.
The project has the following objectives, all contributing to the goal of developing and demonstrating efficacy and applicability of a novel device to transform neuronavigation during brain surgery and cortical activity stimulation:
1) Development of a hyperspectral imaging (HSI) system called HyperProbe to map, monitor and quantify biochemical compounds of interest in brain tissue during neurosurgery and cortical activity stimulation.
2) Industrial upgrade of HyperProbe to a cost-effective, transportable, and compact prototype, that is fully suitable for the neurosurgical room.
3) Characterization and metrological validation of HyperProbe on optically-realistic brain tissue phantoms.
4) Development of machine learning (ML) and artificial intelligence (AI) algorithms to identify biomarkers of brain activity for in vivo imaging with HyperProbe during brain surgery and cortical activity stimulation.
5) Validation of HyperProbe in clinical settings against other surgical imaging standards, such as fMRI and other optical modalities.
6) Conduction of feasibility studies on the performances of the HyperProbe on patients during glioma surgery and multiple paradigms of stimulation of brain activity, as part of observational, proof-of-concept analysis.
The scientific objectives of the project are: (i) multi-disciplinary, merging engineering, physics, computer science, neurology, and neurosurgery; (ii) translational, transforming laboratory-based devices and technology into clinical instrumentation that can be used during brain surgery and in vivo cortical activity stimulation, and (iii) ground-breaking, with potential to critically improve patient and surgical outcomes.
Measuring brain functional activity is of paramount importance during neurosurgery, such as in glioma and glioblastoma (GBM) removal, due to the critical needs for surgeons to: (1) differentiate healthy tissues from tumor/pathological ones; and (2) preserve the integrity of the cerebral functions of the patients intra- and post-surgery. For this reason, brain activity stimulation plays a fundamental role in current neuronavigation approaches for localizing, identifying and assessing areas of cortical and subcortical functions. Several paradigms of brain stimulation are used intraoperatively, mainly depending on which regions of the cortex are targeted, spanning from cognitive tasks on awaken patients (e.g. for speech and visual functions) to electro-stimulation (e.g. for sensorial and motor functions). The latter can be performed in multiple ways, including direct transcortical and/or subcortical stimulation with probes, as well as indirect stimulation and monitoring of muscular responses via electrodes. However, all these types of simulations present limitations, such as different degrees of invasiveness, lack of real-time, quantitative information, reduced specificity and sensitivity. Furthermore, current imaging techniques used to measure brain activity in neurosurgery, either at resting state or during stimulation, are also affected by similar constraints, either (1) being based on static, pre-surgical assessments (e.g. MRI, PET-CT), or (2) for intraoperative modalities (e.g. fluorescence imaging), providing low spatial resolution, low specificity to cerebral functions and limited breadth of information. Overcoming the above-mentioned limitations in neurosurgical planning and management will require to transform and advance current clinical practice towards a functional-guided neuronavigation approach that is capable of providing assistance to neurosurgeons in decision-making with a real-time, quantitative and accurate assessment of brain activity intraoperatively. Therefore, in this project we will design, develop and validate clinically a novel, all-optical, multifunctional imaging device that can lead such transformation and advancement by providing exhaustive characterization of the morpho-chemical features of cerebral tissue during surgery. Such a device can then allow surgeons to access unprecedented functional, structural and pathological information that can improve patient treatment during a number of neurosurgical practices, such as glioma and GBM resection.
The project has the following objectives, all contributing to the goal of developing and demonstrating efficacy and applicability of a novel device to transform neuronavigation during brain surgery and cortical activity stimulation:
1) Development of a hyperspectral imaging (HSI) system called HyperProbe to map, monitor and quantify biochemical compounds of interest in brain tissue during neurosurgery and cortical activity stimulation.
2) Industrial upgrade of HyperProbe to a cost-effective, transportable, and compact prototype, that is fully suitable for the neurosurgical room.
3) Characterization and metrological validation of HyperProbe on optically-realistic brain tissue phantoms.
4) Development of machine learning (ML) and artificial intelligence (AI) algorithms to identify biomarkers of brain activity for in vivo imaging with HyperProbe during brain surgery and cortical activity stimulation.
5) Validation of HyperProbe in clinical settings against other surgical imaging standards, such as fMRI and other optical modalities.
6) Conduction of feasibility studies on the performances of the HyperProbe on patients during glioma surgery and multiple paradigms of stimulation of brain activity, as part of observational, proof-of-concept analysis.
The scientific objectives of the project are: (i) multi-disciplinary, merging engineering, physics, computer science, neurology, and neurosurgery; (ii) translational, transforming laboratory-based devices and technology into clinical instrumentation that can be used during brain surgery and in vivo cortical activity stimulation, and (iii) ground-breaking, with potential to critically improve patient and surgical outcomes.
By the end of the first year of the project, the HyperProbe consortium successfully designed and delivered its first laboratory prototype, HyperProbe1, which aims at guiding the investigation on the optimal parameters and technological features for defining the ultimate clinical devices. Full characterization and preliminary validation of HyperProbe1 is ongoing, with promising initial results on ex vivo fresh surgical biopsies for the identification of novel biomarkers for glioma identification and differentiation. Furthermore, a digital phantom for simulating the optical properties of brain tissue and the implementation of hyperspectral imaging in silico has also been successfully created and tested. This will provide an important metrological tool for the validation and optimization of the hyperspectral technology, in particular Hyperprobe1 and the following clinical prototypes. Ongoing work is currently being carried out also on developing novel software tool based on artificial intelligence to process the hyperspectral data and validation pipelines to compare HyperProbe performances against gold standards in routine neuronavigation.
The technological capacity developed in the project, i.e. the HyperProbe system in the form of a laboratory-based version and a clinical, user-friendly, down-scaled prototype, will impact the neurosurgical field by transforming neuronavigation approaches towards functional imaging-based decision-making. This will be done by overcoming a number of current limitations in the state-of-the-art, particularly thanks to:
◾ Minimal invasiveness of HyperProbe by employing an all-optical, contactless, neuroimaging approach based on the illumination with non-ionizing light of the exposed brain and the measurement of the reflected and fluorescent signals from the cerebral tissues, intraoperatively;
◾ The capacity of HyperProbe of providing real-time, intraoperative information that is quantitative and highly specific to brain tissue activity and structure, via multiple biomarkers related to morpho-chemical features (such as cerebral haemodynamics, metabolism, tumour boundaries, and others);
◾ The high-spatial resolution imaging and specificity provided by HyperProbe to functional, physiological and pathological processes in brain tissue;
◾ The cost-effectiveness, compactness and integration capacity of HyperProbe with current neuronavigation tools in the surgical room which also aims at being transportable and easy-to-use for the clinicians;
◾ The use and application in the HyperProbe of tailored AI and ML algorithms for image reconstruction, image segmentation and for the recognition of morpho-chemical features of interest in the targeted cerebral tissue to be delivered in augmented-reality to the clinicians, intraoperatively.
◾ Minimal invasiveness of HyperProbe by employing an all-optical, contactless, neuroimaging approach based on the illumination with non-ionizing light of the exposed brain and the measurement of the reflected and fluorescent signals from the cerebral tissues, intraoperatively;
◾ The capacity of HyperProbe of providing real-time, intraoperative information that is quantitative and highly specific to brain tissue activity and structure, via multiple biomarkers related to morpho-chemical features (such as cerebral haemodynamics, metabolism, tumour boundaries, and others);
◾ The high-spatial resolution imaging and specificity provided by HyperProbe to functional, physiological and pathological processes in brain tissue;
◾ The cost-effectiveness, compactness and integration capacity of HyperProbe with current neuronavigation tools in the surgical room which also aims at being transportable and easy-to-use for the clinicians;
◾ The use and application in the HyperProbe of tailored AI and ML algorithms for image reconstruction, image segmentation and for the recognition of morpho-chemical features of interest in the targeted cerebral tissue to be delivered in augmented-reality to the clinicians, intraoperatively.