Functional Ultrasound (fUS) During Awake Brain Surgery: The Clinical Potential of Intra-Operative Functional and Vascular Brain Mapping

Background and Purpose: Oncological neurosurgery relies heavily on making continuous, intra-operative tumor-brain delineations based on image-guidance. Limitations of currently available imaging techniques call for the development of real-time image-guided resection tools, which allow for reliable functional and anatomical information in an intra-operative setting. Functional ultrasound (fUS), is a new mobile neuro-imaging tool with unprecedented spatiotemporal resolution, which allows for the detection of small changes in blood dynamics that reflect changes in metabolic activity of activated neurons through neurovascular coupling. We have applied fUS during conventional awake brain surgery to determine its clinical potential for both intra-operative functional and vascular brain mapping, with the ultimate aim of achieving maximum safe tumor resection. Methods: During awake brain surgery, fUS was used to image tumor vasculature and task-evoked brain activation with electrocortical stimulation mapping (ESM) as a gold standard. For functional imaging, patients were presented with motor, language or visual tasks, while the probe was placed over (ESM-defined) functional brain areas. For tumor vascular imaging, tumor tissue (pre-resection) and tumor resection cavity (post-resection) were imaged by moving the hand-held probe along a continuous trajectory over the regions of interest. Results: A total of 10 patients were included, with predominantly intra-parenchymal frontal and temporal lobe tumors of both low and higher histopathological grades. fUS was able to detect (ESM-defined) functional areas deep inside the brain for a range of functional tasks including language processing. Brain tissue could be imaged at a spatial and temporal resolution of 300 μm and 1.5–2.0 ms respectively, revealing real-time tumor-specific, and healthy vascular characteristics. Conclusion: The current study presents the potential of applying fUS during awake brain surgery. We i

Clinical Management and Evolving Novel Therapeutic Strategies for Patients with Brain Tumors

A dramatic increase in knowledge regarding the molecular biology of brain tumors has been established over the past few years, and this has lead to the development of novel therapeutic strategies for these patients. In this book a review of the options available for the clinical management of patients with these tumors are outlined. In addition advances in radiology both for pre-operative diagnostic purposes along with surgical planning are described. Furthermore a review of newer developments in chemotherapy along with the evolving field of photodynamic therapy both for intra-operative management and subsequent therapy is provided. A discussion of certain surgical management issues along with tumor induced epilepsy is included. Finally a discussion of the management of certain unique problems including brain metastases, brainstem glioma, central nervous system lymphoma along with issues involving patients with a brain tumor and pregnancy is provided

Integrated navigation and visualisation for skull base surgery

Skull base surgery involves the management of tumours located on the underside of the brain and the base of the skull. Skull base tumours are intricately associated with several critical neurovascular structures making surgery challenging and high risk. Vestibular schwannoma (VS) is a benign nerve sheath tumour arising from one of the vestibular nerves and is the commonest pathology encountered in skull base surgery. The goal of modern VS surgery is maximal tumour removal whilst preserving neurological function and maintaining quality of life but despite advanced neurosurgical techniques, facial nerve paralysis remains a potentially devastating complication of this surgery. This thesis describes the development and integration of various advanced navigation and visualisation techniques to increase the precision and accuracy of skull base surgery. A novel Diffusion Magnetic Resonance Imaging (dMRI) acquisition and processing protocol for imaging the facial nerve in patients with VS was developed to improve delineation of facial nerve preoperatively. An automated Artificial Intelligence (AI)-based framework was developed to segment VS from MRI scans. A user-friendly navigation system capable of integrating dMRI and tractography of the facial nerve, 3D tumour segmentation and intraoperative 3D ultrasound was developed and validated using an anatomically-realistic acoustic phantom model of a head including the skull, brain and VS. The optical properties of five types of human brain tumour (meningioma, pituitary adenoma, schwannoma, low- and high-grade glioma) and nine different types of healthy brain tissue were examined across a wavelength spectrum of 400 nm to 800 nm in order to inform the development of an Intraoperative Hypserpectral Imaging (iHSI) system. Finally, functional and technical requirements of an iHSI were established and a prototype system was developed and tested in a first-in-patient study

Southwest Research Institute assistance to NASA in biomedical areas of the technology

Significant applications of aerospace technology were achieved. These applications include: a miniaturized, noninvasive system to telemeter electrocardiographic signals of heart transplant patients during their recuperative period as graded situations are introduced; and economical vital signs monitor for use in nursing homes and rehabilitation hospitals to indicate the onset of respiratory arrest; an implantable telemetry system to indicate the onset of the rejection phenomenon in animals undergoing cardiac transplants; an exceptionally accurate current proportional temperature controller for pollution studies; an automatic, atraumatic blood pressure measurement device; materials for protecting burned areas in contact with joint bender splints; a detector to signal the passage of animals by a given point during ecology studies; and special cushioning for use with below-knee amputees to protect the integrity of the skin at the stump/prosthesis interface

From Research to Diagnostic Application of Raman Spectroscopy in Neurosciences: Past and Perspectives

In recent years, Raman spectroscopy has been more and more frequently applied to address research questions in neuroscience. As a non-destructive technique based on inelastic scattering of photons, it can be used for a wide spectrum of applications including neurooncological tumor diagnostics or analysis of misfolded protein aggregates involved in neurodegenerative diseases. Progress in the technical development of this method allows for an increasingly detailed analysis of biological samples and may therefore open new fields of applications. The goal of our review is to provide an introduction into Raman scattering, its practical usage and also commonly associated pitfalls. Furthermore, intraoperative assessment of tumor recurrence using Raman based histology images as well as the search for non-invasive ways of diagnosis in neurodegenerative diseases are discussed. Some of the applications mentioned here may serve as a basis and possibly set the course for a future use of the technique in clinical practice. Covering a broad range of content, this overview can serve not only as a quick and accessible reference tool but also provide more in-depth information on a specific subtopic of interest

Advances in optical molecular imaging for neural visualization

Iatrogenic nerve injury is a significant complication in surgery, which can negatively impact patients’ quality of life. Currently, the main clinical neuroimaging methods, such as computed tomography, magnetic resonance imaging, and high-resolution ultrasonography, do not offer precise real-time positioning images for doctors during surgery. The clinical application of optical molecular imaging technology has led to the emergence of new concepts such as optical molecular imaging surgery, targeted surgery, and molecular-guided surgery. These advancements have made it possible to directly visualize surgical target areas, thereby providing a novel method for real-time identification of nerves during surgery planning. Unlike traditional white light imaging, optical molecular imaging technology enables precise positioning and identifies the cation of intraoperative nerves through the presentation of color images. Although a large number of experiments and data support its development, there are few reports on its actual clinical application. This paper summarizes the research results of optical molecular imaging technology and its ability to realize neural visualization. Additionally, it discusses the challenges neural visualization recognition faces and future development opportunities

Update on the Cytogenetics and Molecular Genetics of Skull Base Chordoma

Chordomas are rare, low-to-intermediate grade malignant tumors arising from notochordal remnants in the midline skeletal axis. They account for <1% of central nervous system tumors and <5% of all primary malignant bone tumors. It is characterized by slow growth, local recurrence, and low metastasis rates. An increasing variety of techniques is now available to detect genetic alterations in chordomas, herein, we review the current knowledge of the genetic alterations in the skull base chordomas. The distribution of copy number changes is composed by two approaches; the low-resolution banding karyotyping and high-resolution whole genome CGH approach. The mapping of candidate genes in chordoma genesis awaits the application of high resolution targeted approaches. Chromosome 1p36.13 and 7q33 represent a candidate region for a chordoma gene. In gene expression study, many genes, such as HER2/neu, epidermal growth factor receptor, c-Met, platelet-derived growth factor receptor A and B, KIT receptors, E-cadherin, neural cell adhesion molecule, progesterone receptor B, estrogen receptor alpha, transforming growth factor alpha and basic fibroblast growth factor, fibronectin, and Cathepsin K, are differentially expressed and act a potential therapeutic targetope

Augmented Reality in Kidney Cancer

Augmented reality(AR) is the concept of a digitally created perception that enhances components of the real-world to allow better engagement with it. Within healthcare, there has been a recent expansion of AR solutions, especially in the field of surgery. Traditional renal cancer surgery has been largely replaced by minimally invasive laparoscopic (or robotic) partial nephrectomies. This has meant loss of certain intra-operative experiences such as haptic feedback and AR can aid this replacement with enhanced visual and patient-specific feedback. The kidney is a dynamic organ and current AR development has revolved around specific surgical stages such as safe arterial clamping and perfecting tumour margins. This chapter discusses the current state of AR technology in these areas with key attention to the aspects of image registration, organ tracking, tissue deformation and live imaging. The chapter then discusses limitations of AR, such as intentional blindness and depth perception and provides potential future ideas and solutions. These include inventions such as AR headsets and 3D-printed renal models (with the possibility of remote surgical intervention). AR provides a very positive outcome for the future of truly minimally invasive renal surgery. However, current AR needs validation, cost evaluation and thorough planning before being safely integrated into everyday surgical practice

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