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

Characterisation of Longitudinal Brain Morphology, Neurometabolism and Prenatal to Neonatal Brain Growth in Patients with Congenital Heart Disease

Congenital heart disease (CHD) affect 8 in 1000 newborns (Liu et al. 2019). The consequences of CHD vary greatly, depending on the specific type of CHD. While advancements in surgical techniques and patient care have led to a high survival rate for severe types of CHD, patients are still at risk of impaired neurodevelopment (ND). Early ND impairment can manifest in various domains, including motor, cognitive or language development (Latal 2016). As a result, one area of CHD research is dedicated to studying the brain development of these patients. This thesis focuses on the longitudinal description of brain development during the late fetal and neonatal period. First, we explored whether deformation-based morphometry (DBM) could be a suitable tool to study CHD patients from fetal to neonatal time period by applying this method to a healthy control cohort. Next, we analysed longitudinally collected data from two studies, primarily focusing on quantifying brain development and searching for associations with ND outcomes in CHD patients. In the first study we explored how DBM could be applied to fetal and neonatal MRI data to observe asymmetry changes during this period. By using DBM, we were able to reveal temporal changes of asymmetry patterns. However, the results may greatly depend on the various combinations of analysis tools and their parameters used. In the second study, where we compared brain development in CHD patients to healthy controls, we therefore relied on volume and surface measurements to quantify growth. Here, we could show that the total brain volume growth trajectory for CHD patients was reduced compared to healthy controls. Finally, we investigated neurometabolite ratios in CHD patients and their association to ND outcome. While we found that a specific neurometabolite ratio (NAA/Cho; N-acetylaspartate to choline-containing compounds) was reduced in the CHD cohort compared to healthy controls, we could not find any association with ND outcome measured at one year of age. In conclusion, the work presented in this thesis uses various methods to study brain development in a longitudinal manner. The findings provide further evidence that brain 4 development in CHD patients is altered while its association with ND outcome requires further investigation

The impact of vestibular modulations on whole brain structure and function in humans

The vestibular system is a sensory system that monitors active and passive headmovements while at the same time permanently sensing gravity. Vestibular information is important for maintaining balance and stabilisation of vision and ultimately for general orientation in space. A distributed set of cortical vestibular regions process vestibular sensory information, together with other sensory and motor signals. How these brain regions are influenced by or interact with each other, and how this depends on the context in which the system is acting is not well understood. In my research I investigated the whole brain consequences of different vestibular sensory contexts by means of structural and functional magnetic resonance (MR) imaging on three different time scales (long-term, short-term, and medium-term). For the long-term time scale, I investigated functional brain connectivity in individuals experiencing a type of chronic dizziness that cannot be explained by structural damage within the nervous system. These patients exhibit chronic or long-term alterations in their processing of vestibular information, which leads to dizziness and vertigo. I found altered sensory and cerebellar network connectivity when they experience a dizziness-provoking stimulus. These two networks contain, but are not limited to, vestibular processing regions, demonstrating the importance of a whole-brain approach. The alterations correspond the notion that these patients have dysfunctional stimulus expectations. The short-term vestibular processing I investigated was the effect of artificial vestibular stimulation, which is frequently used in vestibular research and treatment. For this, I analysed functional network connectivity in healthy participants. I found that short-term vestibular stimulation does not cause a cortical functional reorganisation, although a nociceptive stimulus, which was matched for the somatosensory component of this stimulation, led to a reorganisation. The fact that cortical reorganisation does not occur during exclusively vestibular stimulation may reflect subconscious nature of vestibular processing in that it does not induce a different internal brain state. On the medium-term time scale, I investigated whole-brain structural changes as a result of gravity. Astronauts that travel to space for extended periods of time experience several physiological symptoms also affecting the fluid exchange of the brain. To characterise if these fluid exchanges also affect size of the spaces around brain blood vessels (perivascular spaces), I developed a semi-automatic detection pipeline which requires only one type of structural MR image. I found that space travellers have enlarged perivascular spaces even before their mission, when compared to a control population. These spaces were to a small extend further increased shortly after a long duration space flight of 6 months. Astronaut training thus contributes to structural changes in the whole brain in combination with long-duration space flight. This further suggests that additional contextual factors such as sleep quality should be considered in the future. Overall, in my thesis I show that investigating the whole brain during different vestibular modulations provides additional and novel insights about the underlying neural processes. I found that long-term vestibular states have an impact on functional networks, whilst short-term vestibular modulations do not seem to impact functional network organisation. In addition, I quantified the structural impact of microgravity and astronaut training in the whole brain using a new analysis pipeline. In the future, I expect that new advancements in the field of neuroimaging analysis, such as high sampling of individuals and dynamic network analysis will advance the field. This will potentially also provide new means to monitor disease progression or intervention success

Development of Anatomical and Functional Magnetic Resonance Imaging Measures of Alzheimer Disease

Alzheimer disease is considered to be a progressive neurodegenerative condition, clinically characterized by cognitive dysfunction and memory impairments. Incorporating imaging biomarkers in the early diagnosis and monitoring of disease progression is increasingly important in the evaluation of novel treatments. The purpose of the work in this thesis was to develop and evaluate novel structural and functional biomarkers of disease to improve Alzheimer disease diagnosis and treatment monitoring. Our overarching hypothesis is that magnetic resonance imaging methods that sensitively measure brain structure and functional impairment have the potential to identify people with Alzheimer’s disease prior to the onset of cognitive decline. Since the hippocampus is considered to be one of the first brain structures affected by Alzheimer disease, in our first study a reliable and fully automated approach was developed to quantify medial temporal lobe atrophy using magnetic resonance imaging. This measurement of medial temporal lobe atrophy showed differences (pnovel biomarker of brain activity was developed based on a first-order textural feature of the resting state functional magnetic resonance imagining signal. The mean brain activity metric was shown to be significantly lower (pp18F labeled fluorodeoxyglucose positron emission tomography. In the final study, we examine whether combined measures of gait and cognition could predict medial temporal lobe atrophy over 18 months in a small cohort of people (N=22) with mild cognitive impairment. The results showed that measures of gait impairment can help to predict medial temporal lobe atrophy in people with mild cognitive impairment. The work in this thesis contributes to the growing evidence the specific magnetic resonance imaging measures of brain structure and function can be used to identify and monitor the progression of Alzheimer’s disease. Continued refinement of these methods, and larger longitudinal studies will be needed to establish whether the specific metrics of brain dysfunction developed in this thesis can be of clinical benefit and aid in drug development

Later-life structural and functional consequences of youth exposure to repeated head impacts

Youth football players ages 8-12 may incur hundreds of repeated head impacts (RHI) each season. Evidence suggests concussive brain injury during childhood may disrupt normal developmental processes resulting in long-term impairments. However, little research has investigated the long-term effects of incurring RHI during critical periods of neurodevelopment. Rapid myelination and cerebral blood flow rates, peaks in regional cortical thickness and volumes of specific structures, refinement of regional connectivity, and other neurodevelopmental changes occurring in the brain from ages 10-12 could create a window of vulnerability to RHI. The objective of this research was to determine the relationship between exposure to RHI prior to age 12, during a critical period of neurodevelopment, and later-life brain structure and function. Former National Football League (NFL) players ages 40-65 were divided into two groups based on their age of first exposure (AFE) to RHI through tackle football: AFE <12 and AFE ≥12. In the first study, we observed significantly lower scores on objective tests of executive functioning, memory, and estimated verbal IQ in those who began playing football prior to age 12 compared to those who began playing at age 12 or older. Next, we used diffusion tensor imaging (DTI) to examine the structural integrity of the corpus callosum (CC) and observed that the AFE <12 group had significantly lower fractional anisotropy (FA) as well as a greater decline in FA with age in anterior CC regions than the AFE ≥12 group. Lastly, we used advanced DTI tractography techniques to examine seven CC regions. Significant differences between AFE groups in associations between CC diffusion measures and cognition, mood, and behavior were found. The results of this research suggest that incurring RHI through tackle football during a critical neurodevelopmental period prior to age 12 may result in later-life structural and functional consequences, including cognitive, mood, and behavioral impairments; alterations in white matter structure; and greater vulnerability of white matter to the normal aging process. If replicated with longitudinal designs, larger samples, and athletes whose highest level of play was youth, high school, or college, these findings may have implications for safety recommendations for youth sports

MRI-based brain morphometry correlates of chronic pain in knee osteoarthritis

Chronic pain is a complex experience that involves sensory, emotional, and cognitive aspects. The neurobiological mechanisms are therefore expected to be complex, widespread and largely maladaptive. Recent research of neuroimaging in chronic pain suggests cerebral re-organization on a structural level as a consequence of chronic pain. However, a combined and large-scale brain morphological profile in chronic pain to investigate its neural substrates has not been elucidated. The research presented aims to investigate morphological brain correlates and putatively related behavioural and cognitive aspects of chronic pain due to primary nociceptive knee osteoarthritic disorder using advanced imaging techniques for manual, voxel-based, and surface-based analysis, and questionnaire-based participants’ characterization. 31 participants with chronic painful knee osteoarthritis (age= 64.6± 8.4 years, 15 females, mean duration of pain=9.6 years) and 22 healthy controls (age= 61.3± 7.5, 13 females) underwent high-resolution anatomical MRI at 3 Tesla, and detailed pain characterization and psychometric assessment. Findings from this thesis challenge the common belief that chronic pain leads to hippocampal volume reduction and allegedly cognitive dysfunction. Indeed, general cognitive function and delayed recall memory were normally preserved in the studied cohort, and moreover the hippocampal volume was significantly enlarged. The volume of the rostral part (emotional) of anterior cingulate showed significant positive correlation with pain catastrophizing behaviour suggesting that it may underlie the pain catastrophizing tendency in patients with chronic knee pain. Higher scores of mechanical pain sensitivity correlated with reduced cortical thickness in the anterior cingulate indicating its potential key role in the process of central pain sensitization. Sufferers of chronic knee OA pain exhibited less grey matter volume in the left dorsolateral prefrontal cortex, which has a modulatory role in nociceptive transmission namely, pain perception inhibitory effect. Although the mechanism of this reduction is unknown, such a change may suggest functional disturbance with subsequent aberrant contribution to pain sustainability and chronification. Whole brain cortical thickness was investigated in patients and results revealed wide spread cortical thinning progresses with pain duration, preferentially in females, and in areas largely outside the known pain matrix, but including the posterior default mode network. Finally, preliminary results from investigating the potential mechanism of chronic pain related neocortical plasticity will be presented that may provide framework for future studies

Neuroanatomical correlates of cognitive dysfunction in obstructive sleep apnoea

Obstructive sleep apnoea (OSA) has been reported to be associated with brain hypotrophy and cognitive dysfunction; however, whether these normalise after treatment is unclear. The overall aim of this thesis is to investigate the relationship between OSA and brain structure using FreeSurfer (a new automated technique that reliably measures brain structures). I have investigated changes in brain morphology and the newly described phenomenon in OSA of ischaemic preconditioning. Chapters 4 and 5 will also assess brain structural response to CPAP, and investigate the association between brain structure and cognitive function in OSA. Chapter 3 reports an observational study investigating brain structure. FreeSurfer analysis of magnetic resonance imaging (MRI) found OSA patients had hypertrophy in the right hippocampus (p=0.03) and right choroid plexus (p=0.02) but hypotrophy of the corpus callosum (p=0.04) compared to healthy controls. Chapter 4 reports a randomised controlled trial of CPAP in OSA. At baseline hypotrophy was seen in the corpus callosum (p=0.03) and pallidum (p=0.03) of OSA patients compared to healthy controls. Hypertrophic changes in the right thalamus were seen in the CPAP group after 1 month (p=0.06), associated with improvement in verbal memory (p=0.04). Chapter 5 reports a randomised controlled trial of CPAP in older patients with OSA. A significant decrease in left fimbria volume was seen in the CPAP group (p=0.01). A significant increase in the left presubiculum volume was seen in the best supportive care group (p=0.03). No hippocampal hypertrophy was seen in the CPAP group. In summary, young and middle-aged OSA patients had evidence of brain hypotrophy, but also areas of hypertrophy that may signify dendritic sprouting and increased connectivity as a result of ischaemic preconditioning. This allows recovery of brain hypotrophy after CPAP treatment. This was not seen in older OSA patients suggesting an age-related difference which may have implications for OSA treatment in older people.Open Acces

MRI-based brain morphometry correlates of chronic pain in knee osteoarthritis

Chronic pain is a complex experience that involves sensory, emotional, and cognitive aspects. The neurobiological mechanisms are therefore expected to be complex, widespread and largely maladaptive. Recent research of neuroimaging in chronic pain suggests cerebral re-organization on a structural level as a consequence of chronic pain. However, a combined and large-scale brain morphological profile in chronic pain to investigate its neural substrates has not been elucidated. The research presented aims to investigate morphological brain correlates and putatively related behavioural and cognitive aspects of chronic pain due to primary nociceptive knee osteoarthritic disorder using advanced imaging techniques for manual, voxel-based, and surface-based analysis, and questionnaire-based participants’ characterization. 31 participants with chronic painful knee osteoarthritis (age= 64.6± 8.4 years, 15 females, mean duration of pain=9.6 years) and 22 healthy controls (age= 61.3± 7.5, 13 females) underwent high-resolution anatomical MRI at 3 Tesla, and detailed pain characterization and psychometric assessment. Findings from this thesis challenge the common belief that chronic pain leads to hippocampal volume reduction and allegedly cognitive dysfunction. Indeed, general cognitive function and delayed recall memory were normally preserved in the studied cohort, and moreover the hippocampal volume was significantly enlarged. The volume of the rostral part (emotional) of anterior cingulate showed significant positive correlation with pain catastrophizing behaviour suggesting that it may underlie the pain catastrophizing tendency in patients with chronic knee pain. Higher scores of mechanical pain sensitivity correlated with reduced cortical thickness in the anterior cingulate indicating its potential key role in the process of central pain sensitization. Sufferers of chronic knee OA pain exhibited less grey matter volume in the left dorsolateral prefrontal cortex, which has a modulatory role in nociceptive transmission namely, pain perception inhibitory effect. Although the mechanism of this reduction is unknown, such a change may suggest functional disturbance with subsequent aberrant contribution to pain sustainability and chronification. Whole brain cortical thickness was investigated in patients and results revealed wide spread cortical thinning progresses with pain duration, preferentially in females, and in areas largely outside the known pain matrix, but including the posterior default mode network. Finally, preliminary results from investigating the potential mechanism of chronic pain related neocortical plasticity will be presented that may provide framework for future studies

Libro de actas. XXXV Congreso Anual de la Sociedad Española de Ingeniería Biomédica

596 p.CASEIB2017 vuelve a ser el foro de referencia a nivel nacional para el intercambio científico de conocimiento, experiencias y promoción de la I D i en Ingeniería Biomédica. Un punto de encuentro de científicos, profesionales de la industria, ingenieros biomédicos y profesionales clínicos interesados en las últimas novedades en investigación, educación y aplicación industrial y clínica de la ingeniería biomédica. En la presente edición, más de 160 trabajos de alto nivel científico serán presentados en áreas relevantes de la ingeniería biomédica, tales como: procesado de señal e imagen, instrumentación biomédica, telemedicina, modelado de sistemas biomédicos, sistemas inteligentes y sensores, robótica, planificación y simulación quirúrgica, biofotónica y biomateriales. Cabe destacar las sesiones dedicadas a la competición por el Premio José María Ferrero Corral, y la sesión de competición de alumnos de Grado en Ingeniería biomédica, que persiguen fomentar la participación de jóvenes estudiantes e investigadores