Microscope Embedded Neurosurgical Training and Intraoperative System

In the recent years, neurosurgery has been strongly influenced by new technologies. Computer Aided Surgery (CAS) offers several benefits for patients\u27 safety but fine techniques targeted to obtain minimally invasive and traumatic treatments are required, since intra-operative false movements can be devastating, resulting in patients deaths. The precision of the surgical gesture is related both to accuracy of the available technological instruments and surgeon\u27s experience. In this frame, medical training is particularly important. From a technological point of view, the use of Virtual Reality (VR) for surgeon training and Augmented Reality (AR) for intra-operative treatments offer the best results. In addition, traditional techniques for training in surgery include the use of animals, phantoms and cadavers. The main limitation of these approaches is that live tissue has different properties from dead tissue and that animal anatomy is significantly different from the human. From the medical point of view, Low-Grade Gliomas (LGGs) are intrinsic brain tumours that typically occur in younger adults. The objective of related treatment is to remove as much of the tumour as possible while minimizing damage to the healthy brain. Pathological tissue may closely resemble normal brain parenchyma when looked at through the neurosurgical microscope. The tactile appreciation of the different consistency of the tumour compared to normal brain requires considerable experience on the part of the neurosurgeon and it is a vital point. The first part of this PhD thesis presents a system for realistic simulation (visual and haptic) of the spatula palpation of the LGG. This is the first prototype of a training system using VR, haptics and a real microscope for neurosurgery. This architecture can be also adapted for intra-operative purposes. In this instance, a surgeon needs the basic setup for the Image Guided Therapy (IGT) interventions: microscope, monitors and navigated surgical instruments. The same virtual environment can be AR rendered onto the microscope optics. The objective is to enhance the surgeon\u27s ability for a better intra-operative orientation by giving him a three-dimensional view and other information necessary for a safe navigation inside the patient. The last considerations have served as motivation for the second part of this work which has been devoted to improving a prototype of an AR stereoscopic microscope for neurosurgical interventions, developed in our institute in a previous work. A completely new software has been developed in order to reuse the microscope hardware, enhancing both rendering performances and usability. Since both AR and VR share the same platform, the system can be referred to as Mixed Reality System for neurosurgery. All the components are open source or at least based on a GPL license

The simulation of action disorganisation in complex activities of daily living

Action selection in everyday goal-directed tasks of moderate complexity is known to be subject to breakdown following extensive frontal brain injury. A model of action selection in such tasks is presented and used to explore three hypotheses concerning the origins of action disorganisation: that it is a consequence of reduced top-down excitation within a hierarchical action schema network coupled with increased bottom-up triggering of schemas from environmental sources, that it is a more general disturbance of schema activation modelled by excessive noise in the schema network, and that it results from a general disturbance of the triggering of schemas by object representations. Results suggest that the action disorganisation syndrome is best accounted for by a general disturbance to schema activation, while altering the balance between top-down and bottom-up activation provides an account of a related disorder - utilisation behaviour. It is further suggested that ideational apraxia (which may result from lesions to left temporoparietal areas and which has similar behavioural consequences to action disorganisation syndrome on tasks of moderate complexity) is a consequence of a generalised disturbance of the triggering of schemas by object representations. Several predictions regarding differences between action disorganisation syndrome and ideational apraxia that follow from this interpretation are detailed

Visual saliency and semantic incongruency influence eye movements when inspecting pictures

Models of low-level saliency predict that when we first look at a photograph our first few eye movements should be made towards visually conspicuous objects. Two experiments investigated this prediction by recording eye fixations while viewers inspected pictures of room interiors that contained objects with known saliency characteristics. Highly salient objects did attract fixations earlier than less conspicuous objects, but only in a task requiring general encoding of the whole picture. When participants were required to detect the presence of a small target, then the visual saliency of nontarget objects did not influence fixations. These results support modifications of the model that take the cognitive override of saliency into account by allowing task demands to reduce the saliency weights of task-irrelevant objects. The pictures sometimes contained incongruent objects that were taken from other rooms. These objects were used to test the hypothesis that previous reports of the early fixation of congruent objects have not been consistent because the effect depends upon the visual conspicuity of the incongruent object. There was an effect of incongruency in both experiments, with earlier fixation of objects that violated the gist of the scene, but the effect was only apparent for inconspicuous objects, which argues against the hypothesis

A Behavioural Transformer for Effective Collaboration between a Robot and a Non-stationary Human

A key challenge in human-robot collaboration is the non-stationarity created by humans due to changes in their behaviour. This alters environmental transitions and hinders human-robot collaboration. We propose a principled meta-learning framework to explore how robots could better predict human behaviour, and thereby deal with issues of non-stationarity. On the basis of this framework, we developed Behaviour-Transform (BeTrans). BeTrans is a conditional transformer that enables a robot agent to adapt quickly to new human agents with non-stationary behaviours, due to its notable performance with sequential data. We trained BeTrans on simulated human agents with different systematic biases in collaborative settings. We used an original customisable environment to show that BeTrans effectively collaborates with simulated human agents and adapts faster to non-stationary simulated human agents than SOTA techniques

Modelling glioblastoma tumour-host cell interactions using adult brain organotypic slice co-culture

Glioblastoma multiforme (GBM) is an aggressive incurable brain cancer. The cells that fuel the growth of tumours resemble neural stem cells found in the developing and adult mammalian forebrain. These are referred to as glioma stem cells (GSCs). Similar to neural stem cells, GSCs exhibit a variety of phenotypic states: dormant, quiescent, proliferative and differentiating. How environmental cues within the brain influence these distinct states is not well understood. Laboratory models of GBM can be generated using either genetically engineered mouse models, or via intracranial transplantation of cultured tumour initiating cells (mouse or human). Unfortunately, these approaches are expensive, time-consuming, low-throughput and ill-suited for monitoring live cell behaviours. Here, we explored whole adult brain coronal organotypic slices as an alternative model. Mouse adult brain slices remain viable in a serum-free basal medium for several weeks. GSCs can be easily microinjected into specific anatomical sites ex vivo, and we demonstrate distinct responses of engrafted GSCs to diverse microenvironments in the brain tissue. Within the subependymal zone – one of the adult neural stem cell niches – injected tumour cells could effectively engraft and respond to endothelial niche signals. Tumour-transplanted slices were treated with the antimitotic drug temozolomide as proof of principle of the utility in modelling responses to existing treatments. Engraftment of mouse or human GSCs onto whole brain coronal organotypic brain slices therefore provides a simplified, yet flexible, experimental model. This will help to increase the precision and throughput of modelling GSC-host brain interactions and complements ongoing in vivo studies. This article has an associated First Person interview with the first author of the paper

Modelling and Analysis of a new Integrated Radiofrequency Ablation and Division Device

Master'sMASTER OF ENGINEERIN

Development of an alternative ventricular catheter and an in vitro model of its obstruction

This thesis was previously held under moratorium from 5th November 2014 until 2nd June 2020.Intracranial pressure and volume varies considerably between hydrocephalic patients, and with age, health and haemodynamic status; if left untreated intracranial pressure rises and the ventricular system expands to accommodate the excess cerebrospinal fluid (CSF), with significant morbidity and mortality. Although considerable improvements in design have been made since their introduction all CSF shunts in use today have a high incidence of failure with shunt obstruction being the most serious. Conventional proximal shunt catheters are made from poly (di-methyl) siloxane (PDMS), the walls of which are perforated with holes for the CSF to pass through. The limited range of catheters, in terms of material selection and flow distribution, is responsible in large part for their poor performance.;The aim of the study is to design and fabricate an alternative design of proximal catheter with permeable walls, and to evaluate its performance in the presence of glial cells, which are responsible for blockage. Electrospun Poly-ether Urethane (EPU) samples were fabricated from solvent, by means of an electrospinning technique, to yield microfibrous polymer conduits. The hydrodynamic properties of EPU and conventional shunt were studied using a purpose-built shunt testing system.;The viability and growth of cells on candidate catheter materials such as PDMS and polyurethane in the form of cast films, microfibrous mats and porous sponges were studied in presence of proteins present in CSF after 48h and 96h in culture. The number of viable cells was significantly less on EPU samples compared to the other substrates, which suggests that the fibrous form of the material from which the catheter is made has a bearing on the cell growth. A cell culture model of shunt obstruction was developed in which the cells were subjected to flow during culture in vitro, and the degree of obstruction quantified in terms of hydraulic permeability post static and perfusion culture. The results indicate that a catheter made of EPU would be able to maintain CSF flow even with the presence of cells for the time period chosen for this study. These findings have implications for the design and deployment of micro porous shunt catheter systems for the treatment of hydrocephalus.Intracranial pressure and volume varies considerably between hydrocephalic patients, and with age, health and haemodynamic status; if left untreated intracranial pressure rises and the ventricular system expands to accommodate the excess cerebrospinal fluid (CSF), with significant morbidity and mortality. Although considerable improvements in design have been made since their introduction all CSF shunts in use today have a high incidence of failure with shunt obstruction being the most serious. Conventional proximal shunt catheters are made from poly (di-methyl) siloxane (PDMS), the walls of which are perforated with holes for the CSF to pass through. The limited range of catheters, in terms of material selection and flow distribution, is responsible in large part for their poor performance.;The aim of the study is to design and fabricate an alternative design of proximal catheter with permeable walls, and to evaluate its performance in the presence of glial cells, which are responsible for blockage. Electrospun Poly-ether Urethane (EPU) samples were fabricated from solvent, by means of an electrospinning technique, to yield microfibrous polymer conduits. The hydrodynamic properties of EPU and conventional shunt were studied using a purpose-built shunt testing system.;The viability and growth of cells on candidate catheter materials such as PDMS and polyurethane in the form of cast films, microfibrous mats and porous sponges were studied in presence of proteins present in CSF after 48h and 96h in culture. The number of viable cells was significantly less on EPU samples compared to the other substrates, which suggests that the fibrous form of the material from which the catheter is made has a bearing on the cell growth. A cell culture model of shunt obstruction was developed in which the cells were subjected to flow during culture in vitro, and the degree of obstruction quantified in terms of hydraulic permeability post static and perfusion culture. The results indicate that a catheter made of EPU would be able to maintain CSF flow even with the presence of cells for the time period chosen for this study. These findings have implications for the design and deployment of micro porous shunt catheter systems for the treatment of hydrocephalus

Retrieval from memory: Vulnerable or inviolable?

We show that retrieval from semantic memory is vulnerable even to the mere presence of speech. Irrelevant speech impairs semantic fluency—namely, lexical retrieval cued by a semantic category name—but only if it is meaningful (forward speech compared to reversed speech or words compared to nonwords). Moreover, speech related semantically to the retrieval category is more disruptive than unrelated speech. That phonemic fluency—in which participants are cued with the first letter of words they are to report—was not disrupted by the mere presence of meaningful speech, only by speech in a related phonemic category, suggests that distraction is not mediated by executive processing load. The pattern of sensitivity to different properties of sound as a function of the type of retrieval cue is in line with an interference-by-process approach to auditory distraction