Dynamic Thermal Imaging for Intraoperative Monitoring of Neuronal Activity and Cortical Perfusion

Neurosurgery is a demanding medical discipline that requires a complex interplay of several neuroimaging techniques. This allows structural as well as functional information to be recovered and then visualized to the surgeon. In the case of tumor resections this approach allows more fine-grained differentiation of healthy and pathological tissue which positively influences the postoperative outcome as well as the patient's quality of life. In this work, we will discuss several approaches to establish thermal imaging as a novel neuroimaging technique to primarily visualize neural activity and perfusion state in case of ischaemic stroke. Both applications require novel methods for data-preprocessing, visualization, pattern recognition as well as regression analysis of intraoperative thermal imaging. Online multimodal integration of preoperative and intraoperative data is accomplished by a 2D-3D image registration and image fusion framework with an average accuracy of 2.46 mm. In navigated surgeries, the proposed framework generally provides all necessary tools to project intraoperative 2D imaging data onto preoperative 3D volumetric datasets like 3D MR or CT imaging. Additionally, a fast machine learning framework for the recognition of cortical NaCl rinsings will be discussed throughout this thesis. Hereby, the standardized quantification of tissue perfusion by means of an approximated heating model can be achieved. Classifying the parameters of these models yields a map of connected areas, for which we have shown that these areas correlate with the demarcation caused by an ischaemic stroke segmented in postoperative CT datasets. Finally, a semiparametric regression model has been developed for intraoperative neural activity monitoring of the somatosensory cortex by somatosensory evoked potentials. These results were correlated with neural activity of optical imaging. We found that thermal imaging yields comparable results, yet doesn't share the limitations of optical imaging. In this thesis we would like to emphasize that thermal imaging depicts a novel and valid tool for both intraoperative functional and structural neuroimaging

Anatomical and Functional Organization of Domain-General Brain Regions

How does complex brain activity organize thought and behaviour? Theoretical proposals have long emphasized that intelligent behaviour must be supported by a flexible control system. Numerous brain imaging studies identified a domain-general or “multiple-demand” (MD) brain system co-activated accompanying many tasks and is hypothesised to play a central role in cognitive control. However, the limited spatial localization provided by traditional imaging methods precluded a consensus regarding its anatomy and physiology. To address these limitations, the experiments in chapters 2 and 3 capitalize on novel multi-modal magnetic resonance imaging (MRI) methods developed by the Human Connectome Project. Chapter 2 delineated nine cortical MD patches per hemisphere and subdivided them into 10 regions forming a core of most strongly activated and functionally interconnected regions, surrounded by a penumbra of 17 additional regions. MD activations were also identified in specific subcortical and cerebellar regions. Chapter 3 investigated the relation between the newly defined MD regions and previously identified sensory-biased cortical regions. Contrasting auditory and visual low working memory demands revealed the strongest sensory-biases are localized just outside of MD regions. And additional working memory demands revealed MD activations showed no sensory biases. Chapter 4 used human electrophysiological recordings from the lateral frontal cortex to functionally map cognitive control regions during awake neurosurgeries. By contrasting a hard vs easy cognitive demand, spectral analysis revealed localized power increases in the gamma range (>30 Hz) that overlap with a canonical mask of the fronto-parietal control network. These findings contrast with spatially non-specific power decreases in the beta range (12-30 Hz). Thus, using similar task difficulty manipulations, electrophysiology and MRI functional signals converged on localizing lateral frontal regions related to cognitive control and support their clinical potential for intraoperative mapping of cognitive control. All together, the distributed anatomical organization, mosaic functional preferences, and strong functional interconnectivity of MD regions, suggest a skeleton for integrating and organizing the diverse components of cognitive operations. The precise anatomical delineation of MD regions provides the groundwork for refined analyses of their functions

Enhancing Registration for Image-Guided Neurosurgery

Pharmacologically refractive temporal lobe epilepsy and malignant glioma brain tumours are examples of pathologies that are clinically managed through neurosurgical intervention. The aims of neurosurgery are, where possible, to perform a resection of the surgical target while minimising morbidity to critical structures in the vicinity of the resected brain area. Image-guidance technology aims to assist this task by displaying a model of brain anatomy to the surgical team, which may include an overlay of surgical planning information derived from preoperative scanning such as the segmented resection target and nearby critical brain structures. Accurate neuronavigation is hindered by brain shift, the complex and non-rigid deformation of the brain that arises during surgery, which invalidates assumed rigid geometric correspondence between the neuronavigation model and the true shifted positions of relevant brain areas. Imaging using an interventional MRI (iMRI) scanner in a next-generation operating room can serve as a reference for intraoperative updates of the neuronavigation. An established clinical image processing workflow for iMRI-based guidance involves the correction of relevant imaging artefacts and the estimation of deformation due to brain shift based on non-rigid registration. The present thesis introduces two refinements aimed at enhancing the accuracy and reliability of iMRI-based guidance. A method is presented for the correction of magnetic susceptibility artefacts, which affect diffusion and functional MRI datasets, based on simulating magnetic field variation in the head from structural iMRI scans. Next, a method is presented for estimating brain shift using discrete non-rigid registration and a novel local similarity measure equipped with an edge-preserving property which is shown to improve the accuracy of the estimated deformation in the vicinity of the resected area for a number of cases of surgery performed for the management of temporal lobe epilepsy and glioma

Advancements and Breakthroughs in Ultrasound Imaging

Ultrasonic imaging is a powerful diagnostic tool available to medical practitioners, engineers and researchers today. Due to the relative safety, and the non-invasive nature, ultrasonic imaging has become one of the most rapidly advancing technologies. These rapid advances are directly related to the parallel advancements in electronics, computing, and transducer technology together with sophisticated signal processing techniques. This book focuses on state of the art developments in ultrasonic imaging applications and underlying technologies presented by leading practitioners and researchers from many parts of the world

Translation of Novel Imaging Techniques into Clinical Use for Patients with Epilepsy

Temporal lobe epilepsy is the most common focal epilepsy. Up to 40% of patients are refractory to medication. Anterior temporal lobe resection (ATLR) is an effective treatment but damage to the optic radiation can result in a visual field deficit (VFD) that precludes driving, a key goal of surgery. Diffusion tensor imaging tractography allows the in vivo delineation of white matter tracts such as the optic radiation. This thesis addresses the role of optic radiation tractography in planning and subsequently improving the safety of epilepsy surgery. I show how tractography assists risk stratification and surgical planning in patients with lesions near the optic radiation and assess the utility of different tractography methods for surgical planning. To derive the greatest benefit, tractography information should be available during surgery which requires correction for intraoperative brain shift and other sources of image distortion. I apply software developed at UCL in a clinical population underlying ATLR to show that postoperative imaging can predict the VFD and then use this software in real time during surgery in an intraoperative MRI suite. Updated anatomical scans can be acquired during surgery and tractography data accurately mapped on to these and displayed on the operating microscope display. I demonstrate that this image guidance allows the neurosurgeon to avoid significant VFD without affecting the seizure outcome. Diffusion imaging can also probe tissue microstructure. I explore how structural changes within the frontoparietal working memory network and temporal lobes are related to working memory impairment in TLE. I describe the structural changes that occur following ATLR showing both Wallerian degeneration and structural plasticity. Finally, I show how a novel diffusion model (NODDI) could aid the clinical assessment of patients with focal cortical dysplasia. The emphasis throughout this thesis is how diffusion imaging can be clinically useful and address clinically relevant outcomes

Diffusion imaging and tractography in the paediatric neurosurgical population

Diffusion MRI uses magnetic field gradients to sensitise a MR sequence to in vivo water diffusion. Application of these gradients in specific directions (20 in this work) enables a 3D representation of diffusion on a voxel basis. Quantitative diffusion measures are derived; using the voxel maximal diffusion direction and linking neighbouring voxels iteratively based on this creates a visual construct of the white matter: tractography. It is not possible, currently, to non-invasively determine the histological nature of an intracranial tumour. We recruited paediatric patients with radiological evidence of such lesions from April 2006 to January 2008 and retrospectively to August 2003. We used diffusion MR metrics to discriminate paediatric central nervous system tumours based on existing histological diagnoses. Using apparent diffusion coefficient histograms, common posterior fossa childhood tumours were differentiated with 93% success; Primitive neuroectodermal tumours (PNET) and supratentorial atypical teratoid rhabdoid tumours (ATRT) were separated in 100% of cases. Development of these methods with a larger population may facilitate the obviation of surgical biopsy and its attendant risks. Diffusion data was used to reconstruct the cerebellar white matter anatomy using tractography. Initially a population of normal subjects were investigated using single region of interest (ROI) analysis. DTI metrics were implemented, demonstrating the existence of white matter asymmetry where lateralisation corresponded to handedness in 17 right-handed subjects. To asses functional significance of changes in DTI metrics; clinical cerebellar dysfunction was correlated with changes in cerebellar white matter DTI metrics in a patient population with posterior fossa tumours and with the normal population. Fractional anisotropy of the tracts was reduced in patients with tumours d clinical cerebellar signs as compared to healthy individuals. This work demonstrates that diffusion MRI and tractography metrics may enable discrimination of paediatric CNS tumour type and are related to the functional integrity of cerebellar white matter tracts

Imaging the subthalamic nucleus in Parkinson’s disease

This thesis is comprised of a set of work that aims to visualize and quantify the anatomy, structural variability, and connectivity of the subthalamic nucleus (STN) with optimized neuroimaging methods. The study populations include both healthy cohorts and individuals living with Parkinson's disease (PD). PD was chosen specifically due to the involvement of the STN in the pathophysiology of the disease. Optimized neuroimaging methods were primarily obtained using ultra-high field (UHF) magnetic resonance imaging (MRI). An additional component of this thesis was to determine to what extent UHF-MRI can be used in a clinical setting, specifically for pre-operative planning of deep brain stimulation (DBS) of the STN for patients with advanced PD. The thesis collectively demonstrates that i, MRI research, and clinical applications must account for the different anatomical and structural changes that occur in the STN with both age and PD. ii, Anatomical connections involved in preparatory motor control, response inhibition, and decision-making may be compromised in PD. iii. The accuracy of visualizing and quantifying the STN strongly depends on the type of MR contrast and voxel size. iv, MRI at a field strength of 3 Tesla (T) can under certain circumstances be optimized to produce results similar to that of 7 T at the expense of increased acquisition time