Doctor of Philosophy

dissertationFor many with severe-to-profound hearing loss, a condition in which the cochlea is unable to convert sound vibration into neural information to the brain, the cochlear implant has become the standard treatment. The goal of a cochlear-implant system is to bypass the malfunctioned cochlea and directly stimulate the nerves responsible for hearing through an array of electrodes on a silicone-elastomer carrier. However, the insertion of the electrode arrays can often cause intracochlear damage and eliminate residual hearing. With increased focus on hearing preservation in cochlear implantation, methods to minimize intracochlear damage have become a priority in electrode-array insertions. This dissertation explores the application of magnetic manipulation toward improved cochlear-implant electrode-array insertions. We start with initial 3-to-1 proof-of-concept experiments to demonstrate the feasibility of this approach. Then, to achieve relevancy at clinical scale, lateral-wall-type electrode-array models, used in the clinic, are slightly modified at the tip to include a tiny magnet. Next, a scala-tympani phantom is designed with both simulated cochleostomy and round-window openings to mimic both classes of insertions typically conducted. In particular, this is the first phantom to model a round-window opening and can be used reliably to simulate insertion forces in cadaver cochleae. Electrode arrays are then magnetically guided through these phantoms with a statistically significant (p < 0.05) reduction in insertion forces, and by as much as 50% for some electrode-array models. In particular, guiding the electrode-array tip through the cochlear hook and the basal turn, in the same insertion, was demonstrated for the first time using this technology. All existing methods to guide the electrode array can only be accomplished for the basal turn. Analysis is conducted to determine the optimal size and placement of a magnetic dipole-field source for use in the clinic. Its placement is determined to be consistently lateral to and anterior to the patient’s cochlea. Its size depends on numerous factors including the patient, torque requirements, and registration error. Sensitivity curves summarizing these factors are provided. The volume of the magnetic dipole-field source can be reduced by a factor of 5, on average, by moving it from the modiolar configuration originally proposed to this optimal configuration. We verify that magnetic forces do not pose any appreciable risk to the basilar membrane at the optimal configuration. Although patient-specific optimal configurations are characterized, a one-size-fits-all version is described that may be more practical and carries the benefit of substantial robustness to registration error

Personalized medicine in surgical treatment combining tracking systems, augmented reality and 3D printing

Mención Internacional en el título de doctorIn the last twenty years, a new way of practicing medicine has been focusing on the problems and needs of each patient as an individual thanks to the significant advances in healthcare technology, the so-called personalized medicine. In surgical treatments, personalization has been possible thanks to key technologies adapted to the specific anatomy of each patient and the needs of the physicians. Tracking systems, augmented reality (AR), three-dimensional (3D) printing and artificial intelligence (AI) have previously supported this individualized medicine in many ways. However, their independent contributions show several limitations in terms of patient-to-image registration, lack of flexibility to adapt to the requirements of each case, large preoperative planning times, and navigation complexity. The main objective of this thesis is to increase patient personalization in surgical treatments by combining these technologies to bring surgical navigation to new complex cases by developing new patient registration methods, designing patient-specific tools, facilitating access to augmented reality by the medical community, and automating surgical workflows. In the first part of this dissertation, we present a novel framework for acral tumor resection combining intraoperative open-source navigation software, based on an optical tracking system, and desktop 3D printing. We used additive manufacturing to create a patient-specific mold that maintained the same position of the distal extremity during image-guided surgery as in the preoperative images. The feasibility of the proposed workflow was evaluated in two clinical cases (soft-tissue sarcomas in hand and foot). We achieved an overall accuracy of the system of 1.88 mm evaluated on the patient-specific 3D printed phantoms. Surgical navigation was feasible during both surgeries, allowing surgeons to verify the tumor resection margin. Then, we propose and augmented reality navigation system that uses 3D printed surgical guides with a tracking pattern enabling automatic patient-to-image registration in orthopedic oncology. This specific tool fits on the patient only in a pre-designed location, in this case bone tissue. This solution has been developed as a software application running on Microsoft HoloLens. The workflow was validated on a 3D printed phantom replicating the anatomy of a patient presenting an extraosseous Ewing’s sarcoma, and then tested during the actual surgical intervention. The results showed that the surgical guide with the reference marker can be placed precisely with an accuracy of 2 mm and a visualization error lower than 3 mm. The application allowed physicians to visualize the skin, bone, tumor and medical images overlaid on the phantom and patient. To enable the use of AR and 3D printing by inexperienced users without broad technical knowledge, we designed a step-by-step methodology. The proposed protocol describes how to develop an AR smartphone application that allows superimposing any patient-based 3D model onto a real-world environment using a 3D printed marker tracked by the smartphone camera. Our solution brings AR solutions closer to the final clinical user, combining free and open-source software with an open-access protocol. The proposed guide is already helping to accelerate the adoption of these technologies by medical professionals and researchers. In the next section of the thesis, we wanted to show the benefits of combining these technologies during different stages of the surgical workflow in orthopedic oncology. We designed a novel AR-based smartphone application that can display the patient’s anatomy and the tumor’s location. A 3D printed reference marker, designed to fit in a unique position of the affected bone tissue, enables automatic registration. The system has been evaluated in terms of visualization accuracy and usability during the whole surgical workflow on six realistic phantoms achieving a visualization error below 3 mm. The AR system was tested in two clinical cases during surgical planning, patient communication, and surgical intervention. These results and the positive feedback obtained from surgeons and patients suggest that the combination of AR and 3D printing can improve efficacy, accuracy, and patients’ experience In the final section, two surgical navigation systems have been developed and evaluated to guide electrode placement in sacral neurostimulation procedures based on optical tracking and augmented reality. Our results show that both systems could minimize patient discomfort and improve surgical outcomes by reducing needle insertion time and number of punctures. Additionally, we proposed a feasible clinical workflow for guiding SNS interventions with both navigation methodologies, including automatically creating sacral virtual 3D models for trajectory definition using artificial intelligence and intraoperative patient-to-image registration. To conclude, in this thesis we have demonstrated that the combination of technologies such as tracking systems, augmented reality, 3D printing, and artificial intelligence overcomes many current limitations in surgical treatments. Our results encourage the medical community to combine these technologies to improve surgical workflows and outcomes in more clinical scenarios.Programa de Doctorado en Ciencia y Tecnología Biomédica por la Universidad Carlos III de MadridPresidenta: María Jesús Ledesma Carbayo.- Secretaria: María Arrate Muñoz Barrutia.- Vocal: Csaba Pinte

AUGMENTED REALITY AND INTRAOPERATIVE C-ARM CONE-BEAM COMPUTED TOMOGRAPHY FOR IMAGE-GUIDED ROBOTIC SURGERY

Minimally-invasive robotic-assisted surgery is a rapidly-growing alternative to traditionally open and laparoscopic procedures; nevertheless, challenges remain. Standard of care derives surgical strategies from preoperative volumetric data (i.e., computed tomography (CT) and magnetic resonance (MR) images) that benefit from the ability of multiple modalities to delineate different anatomical boundaries. However, preoperative images may not reflect a possibly highly deformed perioperative setup or intraoperative deformation. Additionally, in current clinical practice, the correspondence of preoperative plans to the surgical scene is conducted as a mental exercise; thus, the accuracy of this practice is highly dependent on the surgeon’s experience and therefore subject to inconsistencies. In order to address these fundamental limitations in minimally-invasive robotic surgery, this dissertation combines a high-end robotic C-arm imaging system and a modern robotic surgical platform as an integrated intraoperative image-guided system. We performed deformable registration of preoperative plans to a perioperative cone-beam computed tomography (CBCT), acquired after the patient is positioned for intervention. From the registered surgical plans, we overlaid critical information onto the primary intraoperative visual source, the robotic endoscope, by using augmented reality. Guidance afforded by this system not only uses augmented reality to fuse virtual medical information, but also provides tool localization and other dynamic intraoperative updated behavior in order to present enhanced depth feedback and information to the surgeon. These techniques in guided robotic surgery required a streamlined approach to creating intuitive and effective human-machine interferences, especially in visualization. Our software design principles create an inherently information-driven modular architecture incorporating robotics and intraoperative imaging through augmented reality. The system's performance is evaluated using phantoms and preclinical in-vivo experiments for multiple applications, including transoral robotic surgery, robot-assisted thoracic interventions, and cocheostomy for cochlear implantation. The resulting functionality, proposed architecture, and implemented methodologies can be further generalized to other C-arm-based image guidance for additional extensions in robotic surgery

Endoscopy

Endoscopy is a fast moving field, and new techniques are continuously emerging. In recent decades, endoscopy has evolved and branched out from a diagnostic modality to enhanced video and computer assisting imaging with impressive interventional capabilities. The modern endoscopy has seen advances not only in types of endoscopes available, but also in types of interventions amenable to the endoscopic approach. To date, there are a lot more developments that are being trialed. Modern endoscopic equipment provides physicians with the benefit of many technical advances. Endoscopy is an effective and safe procedure even in special populations including pediatric patients and renal transplant patients. It serves as the tool for diagnosis and therapeutic interventions of many organs including gastrointestinal tract, head and neck, urinary tract and others

Accurate 3D-reconstruction and -navigation for high-precision minimal-invasive interventions

The current lateral skull base surgery is largely invasive since it requires wide exposure and direct visualization of anatomical landmarks to avoid damaging critical structures. A multi-port approach aiming to reduce such invasiveness has been recently investigated. Thereby three canals are drilled from the skull surface to the surgical region of interest: the first canal for the instrument, the second for the endoscope, and the third for material removal or an additional instrument. The transition to minimal invasive approaches in the lateral skull base surgery requires sub-millimeter accuracy and high outcome predictability, which results in high requirements for the image acquisition as well as for the navigation. Computed tomography (CT) is a non-invasive imaging technique allowing the visualization of the internal patient organs. Planning optimal drill channels based on patient-specific models requires high-accurate three-dimensional (3D) CT images. This thesis focuses on the reconstruction of high quality CT volumes. Therefore, two conventional imaging systems are investigated: spiral CT scanners and C-arm cone-beam CT (CBCT) systems. Spiral CT scanners acquire volumes with typically anisotropic resolution, i.e. the voxel spacing in the slice-selection-direction is larger than the in-the-plane spacing. A new super-resolution reconstruction approach is proposed to recover images with high isotropic resolution from two orthogonal low-resolution CT volumes. C-arm CBCT systems offers CT-like 3D imaging capabilities while being appropriate for interventional suites. A main drawback of these systems is the commonly encountered CT artifacts due to several limitations in the imaging system, such as the mechanical inaccuracies. This thesis contributes new methods to enhance the CBCT reconstruction quality by addressing two main reconstruction artifacts: the misalignment artifacts caused by mechanical inaccuracies, and the metal-artifacts caused by the presence of metal objects in the scanned region. CBCT scanners are appropriate for intra-operative image-guided navigation. For instance, they can be used to control the drill process based on intra-operatively acquired 2D fluoroscopic images. For a successful navigation, accurate estimate of C-arm pose relative to the patient anatomy and the associated surgical plan is required. A new algorithm has been developed to fulfill this task with high-precision. The performance of the introduced methods is demonstrated on simulated and real data

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

Clinical diagnostic utility of transcranial magnetic stimulation in neurological disorders. Updated report of an IFCN committee

The review provides a comprehensive update (previous report: Chen R, Cros D, Curra A, Di Lazzaro V, Lefaucheur JP, Magistris MR, et al. The clinical diagnostic utility of transcranial magnetic stimulation: report of an IFCN committee. Clin Neurophysiol 2008;119(3):504–32) on clinical diagnostic utility of transcranial magnetic stimulation (TMS) in neurological diseases. Most TMS measures rely on stimulation of motor cortex and recording of motor evoked potentials. Paired-pulse TMS techniques, incorporating conventional amplitude-based and threshold tracking, have established clinical utility in neurodegenerative, movement, episodic (epilepsy, migraines), chronic pain and functional diseases. Cortical hyperexcitability has emerged as a diagnostic aid in amyotrophic lateral sclerosis. Single-pulse TMS measures are of utility in stroke, and myelopathy even in the absence of radiological changes. Short-latency afferent inhibition, related to central cholinergic transmission, is reduced in Alzheimer’s disease. The triple stimulation technique (TST) may enhance diagnostic utility of conventional TMS measures to detect upper motor neuron involvement. The recording of motor evoked potentials can be used to perform functional mapping of the motor cortex or in preoperative assessment of eloquent brain regions before surgical resection of brain tumors. TMS exhibits utility in assessing lumbosacral/cervical nerve root function, especially in demyelinating neuropathies, and may be of utility in localizing the site of facial nerve palsies. TMS measures also have high sensitivity in detecting subclinical corticospinal lesions in multiple sclerosis. Abnormalities in central motor conduction time or TST correlate with motor impairment and disability in MS. Cerebellar stimulation may detect lesions in the cerebellum or cerebello-dentatothalamo- motor cortical pathways. Combining TMS with electroencephalography, provides a novel method to measure parameters altered in neurological disorders, including cortical excitability, effective connectivity, and response complexity