Optimization of craniosynostosis surgery: virtual planning, intraoperative 3D photography and surgical navigation

Mención Internacional en el título de doctorCraniosynostosis is a congenital defect defined as the premature fusion of one or more cranial sutures. This fusion leads to growth restriction and deformation of the cranium, caused by compensatory expansion parallel to the fused sutures. Surgical correction is the preferred treatment in most cases to excise the fused sutures and to normalize cranial shape. Although multiple technological advancements have arisen in the surgical management of craniosynostosis, interventional planning and surgical correction are still highly dependent on the subjective assessment and artistic judgment of craniofacial surgeons. Therefore, there is a high variability in individual surgeon performance and, thus, in the surgical outcomes. The main objective of this thesis was to explore different approaches to improve the surgical management of craniosynostosis by reducing subjectivity in all stages of the process, from the preoperative virtual planning phase to the intraoperative performance. First, we developed a novel framework for automatic planning of craniosynostosis surgery that enables: calculating a patient-specific normative reference shape to target, estimating optimal bone fragments for remodeling, and computing the most appropriate configuration of fragments in order to achieve the desired target cranial shape. Our results showed that automatic plans were accurate and achieved adequate overcorrection with respect to normative morphology. Surgeons’ feedback indicated that the integration of this technology could increase the accuracy and reduce the duration of the preoperative planning phase. Second, we validated the use of hand-held 3D photography for intraoperative evaluation of the surgical outcome. The accuracy of this technology for 3D modeling and morphology quantification was evaluated using computed tomography imaging as gold-standard. Our results demonstrated that 3D photography could be used to perform accurate 3D reconstructions of the anatomy during surgical interventions and to measure morphological metrics to provide feedback to the surgical team. This technology presents a valuable alternative to computed tomography imaging and can be easily integrated into the current surgical workflow to assist during the intervention. Also, we developed an intraoperative navigation system to provide real-time guidance during craniosynostosis surgeries. This system, based on optical tracking, enables to record the positions of remodeled bone fragments and compare them with the target virtual surgical plan. Our navigation system is based on patient-specific surgical guides, which fit into the patient’s anatomy, to perform patient-to-image registration. In addition, our workflow does not rely on patient’s head immobilization or invasive attachment of dynamic reference frames. After testing our system in five craniosynostosis surgeries, our results demonstrated a high navigation accuracy and optimal surgical outcomes in all cases. Furthermore, the use of navigation did not substantially increase the operative time. Finally, we investigated the use of augmented reality technology as an alternative to navigation for surgical guidance in craniosynostosis surgery. We developed an augmented reality application to visualize the virtual surgical plan overlaid on the surgical field, indicating the predefined osteotomy locations and target bone fragment positions. Our results demonstrated that augmented reality provides sub-millimetric accuracy when guiding both osteotomy and remodeling phases during open cranial vault remodeling. Surgeons’ feedback indicated that this technology could be integrated into the current surgical workflow for the treatment of craniosynostosis. To conclude, in this thesis we evaluated multiple technological advancements to improve the surgical management of craniosynostosis. The integration of these developments into the surgical workflow of craniosynostosis will positively impact the surgical outcomes, increase the efficiency of surgical interventions, and reduce the variability between surgeons and institutions.Programa de Doctorado en Ciencia y Tecnología Biomédica por la Universidad Carlos III de MadridPresidente: Norberto Antonio Malpica González.- Secretario: María Arrate Muñoz Barrutia.- Vocal: Tamas Ung

Real-time intrafraction motion monitoring in external beam radiotherapy

© 2019 Institute of Physics and Engineering in Medicine. Radiotherapy (RT) aims to deliver a spatially conformal dose of radiation to tumours while maximizing the dose sparing to healthy tissues. However, the internal patient anatomy is constantly moving due to respiratory, cardiac, gastrointestinal and urinary activity. The long term goal of the RT community to 'see what we treat, as we treat' and to act on this information instantaneously has resulted in rapid technological innovation. Specialized treatment machines, such as robotic or gimbal-steered linear accelerators (linac) with in-room imaging suites, have been developed specifically for real-time treatment adaptation. Additional equipment, such as stereoscopic kilovoltage (kV) imaging, ultrasound transducers and electromagnetic transponders, has been developed for intrafraction motion monitoring on conventional linacs. Magnetic resonance imaging (MRI) has been integrated with cobalt treatment units and more recently with linacs. In addition to hardware innovation, software development has played a substantial role in the development of motion monitoring methods based on respiratory motion surrogates and planar kV or Megavoltage (MV) imaging that is available on standard equipped linacs. In this paper, we review and compare the different intrafraction motion monitoring methods proposed in the literature and demonstrated in real-time on clinical data as well as their possible future developments. We then discuss general considerations on validation and quality assurance for clinical implementation. Besides photon RT, particle therapy is increasingly used to treat moving targets. However, transferring motion monitoring technologies from linacs to particle beam lines presents substantial challenges. Lessons learned from the implementation of real-time intrafraction monitoring for photon RT will be used as a basis to discuss the implementation of these methods for particle RT

Expanding the use of real-time electromagnetic tracking in radiation oncology.

In the past 10 years, techniques to improve radiotherapy delivery, such as intensity-modulated radiation therapy (IMRT), image-guided radiation therapy (IGRT) for both inter- and intrafraction tumor localization, and hypofractionated delivery techniques such as stereotactic body radiation therapy (SBRT), have evolved tremendously. This review article focuses on only one part of that evolution, electromagnetic tracking in radiation therapy. Electromagnetic tracking is still a growing technology in radiation oncology and, as such, the clinical applications are limited, the expense is high, and the reimbursement is insufficient to cover these costs. At the same time, current experience with electromagnetic tracking applied to various clinical tumor sites indicates that the potential benefits of electromagnetic tracking could be significant for patients receiving radiation therapy. Daily use of these tracking systems is minimally invasive and delivers no additional ionizing radiation to the patient, and these systems can provide explicit tumor motion data. Although there are a number of technical and fiscal issues that need to be addressed, electromagnetic tracking systems are expected to play a continued role in improving the precision of radiation delivery

Advanced cranial navigation

Neurosurgery is performed with extremely low margins of error. Surgical inaccuracy may have disastrous consequences. The overall aim of this thesis was to improve accuracy in cranial neurosurgical procedures by the application of new technical aids. Two technical methods were evaluated: augmented reality (AR) for surgical navigation (Papers I-II) and the optical technique of diffuse reflectance spectroscopy (DRS) for real-time tissue identification (Papers III-V). Minimally invasive skull-base endoscopy has several potential benefits compared to traditional craniotomy, but approaching the skull base through this route implies that at-risk organs and surgical targets are covered by bone and out of the surgeon’s direct line of sight. In Paper I, a new application for AR-navigated endoscopic skull-base surgery, based on an augmented-reality surgical navigation (ARSN) system, was developed. The accuracy of the system, defined by mean target registration error (TRE), was evaluated and found to be 0.55±0.24 mm, the lowest value reported error in the literature. As a first step toward the development of a cranial application for AR navigation, in Paper II this ARSN system was used to enable insertions of biopsy needles and external ventricular drainages (EVDs). The technical accuracy (i.e., deviation from the target or intended path) and efficacy (i.e., insertion time) were assessed on a 3D-printed realistic, anthropomorphic skull and brain phantom; Thirty cranial biopsies and 10 EVD insertions were performed. Accuracy for biopsy was 0.8±0.43 mm with a median insertion time of 149 (87-233) seconds, and for EVD accuracy was 2.9±0.8 mm at the tip with a median angular deviation of 0.7±0.5° and a median insertion time of 188 (135-400) seconds. Glial tumors grow diffusely in the brain, and patient survival is correlated with the extent of tumor removal. Tumor borders are often invisible. Resection beyond borders as defined by conventional methods may further improve a patient’s prognosis. In Paper III, DRS was evaluated for discrimination between glioma and normal brain tissue ex vivo. DRS spectra and histology were acquired from 22 tumor samples and 9 brain tissue samples retrieved from 30 patients. Sensitivity and specificity for the detection of low-grade gliomas were 82.0% and 82.7%, respectively, with an AUC of 0.91. Acute ischemic stroke caused by large vessel occlusion is treated with endovascular thrombectomy, but treatment failure can occur when clot composition and thrombectomy technique are mismatched. Intra-procedural knowledge of clot composition could guide the choice of treatment modality. In Paper IV, DRS, in vivo, was evaluated for intravascular clot characterization. Three types of clot analogs, red blood cell (RBC)-rich, fibrin-rich and mixed clots, were injected into the external carotids of a domestic pig. An intravascular DRS probe was used for in-situ measurements of clots, blood, and vessel walls, and the spectral data were analyzed. DRS could differentiate clot types, vessel walls, and blood in vivo (p<0,001). The sensitivity and specificity for detection were 73.8% and 98.8% for RBC clots, 100% and 100% for mixed clots, and 80.6% and 97.8% for fibrin clots, respectively. Paper V evaluated DRS for characterization of human clot composition ex vivo: 45 clot units were retrieved from 29 stroke patients and examined with DRS and histopathological evaluation. DRS parameters correlated with clot RBC fraction (R=81, p<0.001) and could be used for the classification of clot type with sensitivity and specificity rates for the detection of RBC-rich clots of 0.722 and 0.846, respectively. Applied in an intravascular probe, DRS may provide intra-procedural information on clot composition to improve endovascular thrombectomy efficiency

Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 165, March 1977

This bibliography lists 198 reports, articles, and other documents introduced into the NASA scientific and technical information system in February 1977

Reducing Uncertainty in Head and Neck Radiotherapy with Plastic Robotics

One of the greatest challenges in achieving accurate positioning in head and neck radiotherapy is that the anatomy at and above the cervical spine does not act as a single, mechanically rigid body. Current immobilization techniques contain residual uncertainties that are especially present in the lower neck that cannot be reduced by setting up to any single landmark. The work presented describes the development of a radiotherapy friendly mostly-plastic 6D robotic platform for positioning independent landmarks, (i.e., allowing remote, independent positioning of the skull relative to landmarks in the thorax), including analysis of kinematics, stress, radiographic compatibility, trajectory planning, physical construction, and phantom measurements of correction accuracy. No major component of the system within the field of imaging or treatment had a measured attenuation value greater than 250 HU, showing compatibility with x-ray-based imaging techniques. Relative to arbitrary overall setup errors of the head (min = 1.1 mm, max = 5.2 mm vector error) the robotic platform corrected the position down to a residual overall error of 0.75 mm +/- 0.33 mm over 15 cases as measured with optical tracking. This device shows the potential for providing reductions to dose margins in head and neck therapy cases, while also reducing setup time and effort

Computational ultrasound tissue characterisation for brain tumour resection

In brain tumour resection, it is vital to know where critical neurovascular structuresand tumours are located to minimise surgical injuries and cancer recurrence. Theaim of this thesis was to improve intraoperative guidance during brain tumourresection by integrating both ultrasound standard imaging and elastography in thesurgical workflow. Brain tumour resection requires surgeons to identify the tumourboundaries to preserve healthy brain tissue and prevent cancer recurrence. Thisthesis proposes to use ultrasound elastography in combination with conventionalultrasound B-mode imaging to better characterise tumour tissue during surgery.Ultrasound elastography comprises a set of techniques that measure tissue stiffness,which is a known biomarker of brain tumours. The objectives of the researchreported in this thesis are to implement novel learning-based methods for ultrasoundelastography and to integrate them in an image-guided intervention framework.Accurate and real-time intraoperative estimation of tissue elasticity can guide towardsbetter delineation of brain tumours and improve the outcome of neurosurgery. We firstinvestigated current challenges in quasi-static elastography, which evaluates tissuedeformation (strain) by estimating the displacement between successive ultrasoundframes, acquired before and after applying manual compression. Recent approachesin ultrasound elastography have demonstrated that convolutional neural networkscan capture ultrasound high-frequency content and produce accurate strain estimates.We proposed a new unsupervised deep learning method for strain prediction, wherethe training of the network is driven by a regularised cost function, composed of asimilarity metric and a regularisation term that preserves displacement continuityby directly optimising the strain smoothness. We further improved the accuracy of our method by proposing a recurrent network architecture with convolutional long-short-term memory decoder blocks to improve displacement estimation and spatio-temporal continuity between time series ultrasound frames. We then demonstrateinitial results towards extending our ultrasound displacement estimation method toshear wave elastography, which provides a quantitative estimation of tissue stiffness.Furthermore, this thesis describes the development of an open-source image-guidedintervention platform, specifically designed to combine intra-operative ultrasoundimaging with a neuronavigation system and perform real-time ultrasound tissuecharacterisation. The integration was conducted using commercial hardware andvalidated on an anatomical phantom. Finally, preliminary results on the feasibilityand safety of the use of a novel intraoperative ultrasound probe designed for pituitarysurgery are presented. Prior to the clinical assessment of our image-guided platform,the ability of the ultrasound probe to be used alongside standard surgical equipmentwas demonstrated in 5 pituitary cases