Optimized and integrated alignment system for functional proton radiosurgery

In this thesis work, a system for proton beam alignment was studied and optimized in many of its functional areas. The resulting system was named Positioning Alignment Control System (PACS). The PACS system is an integrated and efficient system as a result of the work done on it in the course of this thesis work

Software-based gradient nonlinearity distortion correction

The primary purpose of the thesis is to discuss the use of Magnetic Resonance Imaging (MRI) in functional proton radiosurgery. The methods presented in this thesis were specifically designed to correct gradient nonlinearity distortion, the single greatest hurdle that limits the deployment of MRI-based functional proton radiosurgery systems. The new system central in the thesis fully utilized MRI to provide localization of anatomical targets with submillimeter accuracy. The thesis provides analysis and solutions to the problems related to gradient nonlinearity distortion. The characteristics of proton radiosurgery are introduced, in addition to a discussion of its advantages over other current methods of radiation oncology. A historical background for proton radiosurgery is also presented, along with a description of its implementation at Loma Linda University Medical Center (LLUMC), where a new system for functional proton radiosurgery has been proposed and is currently under development

Towards development of automatic path planning system in image-guided neurosurgery

With the advent of advanced computer technology, many computer-aided systems have evolved to assist in medical related work including treatment, diagnosis, and even surgery. In modern neurosurgery, Magnetic Resonance Image guided stereotactic surgery exactly complies with this trend. It is a minimally invasive operation being much safer than the traditional open-skull surgery, and offers higher precision and more effective operating procedures compared to conventional craniotomy. However, such operations still face significant challenges of planning the optimal neurosurgical path in order to reach the ideal position without damage to important internal structures. This research aims to address this major challenge. The work begins with an investigation of the problem of distortion induced by MR images. It then goes on to build a template of the Circle of Wills brain vessels, realized from a collection of Magnetic Resonance Angiography images, which is needed to maintain operating standards when, as in many cases, Magnetic Resonance Angiography images are not available for patients. Demographic data of brain tumours are also studied to obtain further understanding of diseased human brains through the development of an effect classifier. The developed system allows the internal brain structure to be ‘seen’ clearly before the surgery, giving surgeons a clear picture and thereby makes a significant contribution to the eventual development of a fully automatic path planning system

Development of quality control protocol and software tool for the correction of geometric distortions and signal inhomogeneities in magnetic resonance images

Η Απεικόνιση Μαγνητικού Συντονισμού (ΑΜΣ) χρησιμοποιείται ευρύτατα στις σύγχρονες ακτινοθεραπευτικές εφαρμογές και ιδιαίτερα στο σχεδιασμό πλάνου θεραπείας στη Στερεοτακτική Ακτινοχειρουργική (ΣΑ) για ενδοκρανιακές θεραπείες. Η επιλογή αυτή δικαιολογείται από την εξαιρετική αντίθεση μαλακού ιστού που προσφέρει η ΑΜΣ σε σχέση με την Υπολογιστική Τομογραφία (ΥΤ) καθώς επίσης και την ευελιξία στην αντίθεση εικόνας. Έτσι, με τη βοήθεια εικόνων ΑΜΣ επιτυγχάνεται καλύτερη περιγραφή και χαρακτηρισμός του όγκου-στόχου. Ειδικότερα για θεραπείες εγκεφαλικών μεταστάσεων και άλλων βλαβών, η ΑΜΣ αποτελεί την πρώτη επιλογή απεικονιστικής τεχνικής τόσο για τον όγκο-στόχο όσο και τους υγιείς ιστούς. Αυτή η επιλογή όμως έρχεται σε βάρος της γεωμετρικής ακρίβειας καθώς είναι ευρέως γνωστό ότι οι εικόνες ΑΜΣ φέρουν γεωμετρική παραμόρφωση. Μετά από μία σύντομη παράθεση του σχετικού θεωρητικού υποβάθρου, στο δεύτερο μέρος της παρούσας εργασίας διενεργήθηκε αξιολόγηση των γεωμετρικών παραμορφώσεων που σχετίζονται με τις εικόνες ΑΜΣ. Για το σκοπό αυτό, σχεδιάστηκε και κατασκευάστηκε ένα ειδικό ομοίωμα για τον χαρακτηρισμό τους και εφαρμόστηκε σε ακολουθίες και παραμέτρους απεικόνισης ΑΜΣ που χρησιμοποιούνται κλινικά κατά το σχεδιασμό πλάνου θεραπείας στην ΣΑ, σύμφωνα με πρωτόκολλα θεραπείας που βασίζονται είτε στην ΑΜΣ μόνο, είτε επικουρικά. Το ομοίωμα φέρει 947 σημεία ελέγχου (ΣΕ) και σχεδιάστηκε ώστε να είναι συμβατό με το πηνίο κεφαλής καθώς και το Leksell στερεοτακτικό πλαίσιο που χρησιμοποιείται για την ακινητοποίηση του ασθενούς και τον ορισμό του στερεοτακτικού χώρου σε εφαρμογές ΣΑ. Οι παραμορφώσεις που επάγονται από το σύστημα αξιολογήθηκαν με και χωρίς την παρουσία του στερεοτακτικού πλαισίου. Μετά από απαλοιφή των παραμορφώσεων που σχετίζονται με τις ανομοιογένειες του στατικού μαγνητικού πεδίου, απουσία του στερεοτακτικού πλαισίου η μετρούμενη μέση παραμόρφωση που σχετίζεται με τη μη-γραμμικότητα των βαθμιδωτών πεδίων ήταν 0.53 mm. Αντίθετα, παρουσία του πλαισίου, ανιχνεύθηκε αύξηση της παραμόρφωσης αυτής (μέχρι και 5 mm) στην περιοχή γύρω από τη βάση του πλαισίου, λόγω των δεινορευμάτων που επάγονται στον κλειστό της βρόγχο από αλουμίνιο. Αν και η περιοχή μέγιστης παραμόρφωσης δεν βρίσκεται εντός του όγκου που μπορεί να ακτινοβοληθεί με ΣΑ, η εν λόγω παραμόρφωση εξαλείφεται σε απόσταση περίπου 90 mm από τη βάση του πλαισίου. Οι έντονες παραμορφώσεις που παρατηρήθηκαν εκτός του όγκου που δύναται να ακτινοβοληθεί, μπορεί όμως να υποβαθμίσουν την ακρίβεια ακτινοβόλησης μέσω του επηρεασμού της χωρικής ευθυγράμμισης (π.χ., η θέση του κατώτερου μέρους του ειδικού σημαδιού σχήματος Ν που ορίζει τον στερεοτακτικό χώρο μπορεί να είναι χωρικά στρεβλωμένο). Οι παραμορφώσεις που σχετίζονται με το σύστημα απεικόνισης ανιχνεύθηκαν και σε εικόνες ασθενούς. Χρησιμοποιώντας αγγειογραφία ΥΤ ως εικόνα αναφοράς του ασθενούς, μια απόκλιση 1.1 mm εντοπίστηκε σε δύο αγγεία που βρίσκονται σε μικρή απόσταση από τη βάση του πλαισίου, ενώ εξαιρετική χωρική συμφωνία είχε ένα άλλο αγγείο ευρισκόμενο σε μεγάλη απόσταση από αυτήν. Το ίδιο ομοίωμα απεικονίστηκε σε 1.5 και 3.0Τ με χρήση τριών διαφορετικών κλινικών πρωτοκόλλων ΑΜΣ για χρήση σε σχεδιασμό πλάνου θεραπείας στην ΣΑ. Αξιολογήθηκαν οι παραμορφώσεις που σχετίζονται με την ανομοιογένεια του Β0 μαγνητικού πεδίου και τη μη-γραμμικότητα των βαθμιδωτών πεδίων. Περιοχές αυξημένης παραμόρφωσης καταγράφηκαν στις παρυφές του χαρτογραφούμενου όγκου, ο οποίος ήταν συγκρίσιμος με μια τυπική σάρωση κεφαλής. Αν και η μέση απόλυτη παραμόρφωση δεν ξεπέρασε τα 0.5 mm σε κανένα χωρικό άξονα, η μέγιστη απόκλιση ΣΕ έφτασε τα 2 mm. Στη συνέχεια, το ομοίωμα τροποποιήθηκε καταλλήλως ώστε να φέρει δύο κυλινδρικές δομές που προσομοιάζουν εγκεφαλικές μεταστάσεις. Οι δομές γεμίστηκαν με διάφορες συγκεντρώσεις (0-20 mM) του σκιαγραφικού Gd-DTPA (συχνά χορηγούμενο στην ΑΜΣ για ΣΑ εγκεφάλου) με σκοπό τον χαρακτηρισμό των παραμορφώσεων που επάγονται από το ίδιο το σκιαγραφικό. Η μέθοδος αναστροφής της πολικότητας της βαθμίδας κωδικοποίησης της συχνότητας συνδυάστηκε με την τεχνική χαρτογράφησης πεδίου ώστε να είναι δυνατός ο διαχωρισμός μεταξύ των πηγών παραμόρφωσης. Το σκιαγραφικό βρέθηκε ότι επηρεάζει σημαντικά τη θέση των δομών, με την απόκλιση να φτάνει κατά μέσο όρο τα 0.067 mm/mM (0.204 ppm/mM). Μετά από χορήγηση κλινικής δόσης του ίδιου σκιαγραφικού, εικόνες ΑΜΣ ασθενών με συνολικά 10 εγκεφαλικές μεταστάσεις/στόχους μελετήθηκαν εφαρμόζοντας παρόμοια μεθοδολογία. Η συνολική αβεβαιότητα στο χωρικό εντοπισμό των όγκων ήταν κατά μέσο όρο 0.54 mm (2.24 ppm) για το πρωτόκολλο ΑΜΣ που χρησιμοποιήθηκε, σε συμφωνία με τα αποτελέσματα του ομοιώματος. Σε μια προσπάθεια να καθοριστεί ποια γεωμετρική αβεβαιότητα μπορεί να είναι ανεκτή, πλάνα θεραπείας υψηλής συμμόρφωσης χρησιμοποιήθηκαν για την προσομοίωση ακτινοβόλησης στόχων διαφόρων διαμέτρων (5 έως 50 mm). Χωρικές μεταθέσεις από 0.5 έως 3 mm εφαρμόστηκαν εσκεμμένα στους στόχους. Στη συνέχεια, υπολογίστηκαν ιστογράμματα δόσης-όγκου και δείκτες ποιότητας πλάνου που χρησιμοποιούνται κλινικά για την αξιολόγηση και αποδοχή πλάνων θεραπείας. Τα αποτελέσματα χρησιμοποιήθηκαν για τη διερεύνηση της επιρροής της γεωμετρικής αβεβαιότητας (παραμόρφωσης) στην ακρίβεια της εναπόθεσης της δόσης και στην ποιότητα του πλάνου. Η τελευταία βρέθηκε ότι εξαρτάται ισχυρά από τις διαστάσεις του στόχου. Για στόχους μικρότερους των 20 mm σε διάμετρο, μια χωρική μετατόπιση της τάξης του 1 mm μπορεί να επιφέρει σημαντική μεταβολή (>5%) στα κριτήρια ποιότητας/αποδοχής του πλάνου. Για στόχους διαμέτρου πάνω από 2 cm, η αντίστοιχη μετατόπιση βρέθηκε ότι είναι πάνω από 1.5 mm. Στο τελευταίο μέρος αυτής της εργασίας, αξιολογήθηκαν ή/και αναπτύχθηκαν τεχνικές και αλγόριθμοι διόρθωσης της γεωμετρικής παραμόρφωσης. Συγκεκριμένα, η αποτελεσματικότητα των αλγορίθμων διόρθωσης (μόνο για τη μη-γραμμικότητα βαθμίδων) που παρέχονται από τους κατασκευαστές αξιολογήθηκε αρχικά για ποικιλία συστημάτων ΑΜΣ, μετά από το σχεδιασμό και κατασκευή μιας εξελιγμένης έκδοσης του ομοιώματος χαρτογράφησης παραμόρφωσης, με υψηλή διακριτική ικανότητα, το οποίο φέρει σχεδόν 2000 ΣΕ. Επίσης, η μεθοδολογία διόρθωσης μέσης-εικόνας αναπτύχθηκε και αξιολογήθηκε τόσο σε εικόνες ομοιώματος όσο και σε ασθενών. Η προτεινόμενη τεχνική βασίζεται στη μέθοδο αναστροφής της πολικότητας και για το λόγο αυτό απαιτεί δύο σαρώσεις ΑΜΣ. Συγκεκριμένα, η νέα εικόνα συντίθεται από τις μέσες τιμές των εντάσεων σήματος των αντίστοιχων εικόνων αντίθετης πολικότητας, υπολογισμένες πίξελ-προς-πίξελ. Η μέθοδος διόρθωσης αυτή βρέθηκε αποδοτική στην ελαχιστοποίηση παραμορφώσεων που εξαρτώνται από την ακολουθία που χρησιμοποιείται. Επιπλέον, διεξήχθη μια συγκριτική μελέτη που περιλάμβανε την πιο καλά καθιερωμένη μέθοδο διόρθωσης που βασίζεται στην ολοκλήρωση του σήματος, αφού αναπτύχθηκαν όλες οι απαραίτητες σχετικές ρουτίνες για την εφαρμογή της. Και οι δύο μέθοδοι διόρθωσης βρέθηκαν να αποδίδουν εξίσου καλά, ελαχιστοποιώντας τη μέση και διάμεσο εναπομείνουσα παραμόρφωση. Η μέθοδος ολοκλήρωσης σήματος, όμως, απαιτεί μερικές ώρες υπολογιστικού χρόνου μετά τη λήψη των εικόνων, ενώ η μέση-εικόνα είναι πιο αποδοτική και πιο απλή στην εφαρμογή της.Magnetic Resonance Imaging (MRI) is widely used in advanced radiotherapy applications and, especially, in stereotactic radiosurgery (SRS) treatment planning for intracranial applications. This is justified by the superior soft tissue contrast it exhibits as compared to Computed Tomography (CT) and its multi-contrast capability, which result in better tumor delineation and characterization. Especially for brain lesions, MRI has been established as the imaging modality of choice for both target and normal tissue delineation. This choice, however, comes at the expense of geometric accuracy since it is well known that MR images are geometrically distorted. Following an analysis of the underlying theoretical background, in the second part of this thesis an evaluation of the MR-related geometric distortions is performed. To this end, a prototype phantom was designed and constructed to facilitate distortion characterization for the MR pulse sequences and imaging parameters clinically employed in SRS treatment planning, in MRI-based or MRI-only protocols. The phantom incorporates 947 Control Points (CPs) and was designed to accurately fit in a typical head coil, as well as the Leksell stereotactic frame, used for patient immobilization in SRS applications. System-related distortions were characterized both with and without the presence of the frame. In the absence of the frame and following compensation for field inhomogeneities, measured average CP displacement owing to gradient nonlinearities was 0.53 mm. In presence of the frame, contrarily, detected distortion was greatly increased (up to about 5 mm) in the vicinity of the frame base due to eddy currents induced in the closed loop of its aluminum material. Although the region with the maximum observed distortion may not lie within the SRS treatable volume, frame-related distortion was obliterated at approximately 90 mm from the frame base. Severe distortions observed outside the treatable volume could possibly impinge on the delivery accuracy mainly by adversely affecting the registration process (e.g., the position of the lower part of the N-shaped fiducials used to define the stereotactic space may be miss-registered). System-related distortion was also identified in patient MR images. Using corresponding CT angiography images as a reference, an offset of 1.1 mm was detected for two vessels lying in close proximity to the frame base, while excellent spatial agreement was observed for a vessel far apart from the frame base. The same phantom was scanned at 1.5 and 3.0T and using three clinical MR imaging protocols for SRS treatment planning. B0 inhomogeneity and gradient nonlinearity related geometric distortions were assessed in this study. Areas of increased distortion were identified at the edges of the imaged volume which was comparable to a brain scan. Although mean absolute distortion did not exceed 0.5 mm on any spatial axis, maximum detected CP displacement reached 2 mm. Furthermore, the phantom was modified to incorporate two cylindrical inserts, simulating small brain metastases. The inserts were filled with various concentrations (0-20 mM) of Gd-DTPA (commonly administered in cranial SRS) in order to characterize contrast agent induced distortion. The reversed read gradient polarity was combined with the field mapping technique to distinguish between sources of distortion. Contrast agent was found to significantly affect insert position, with the centroid offset reaching on average 0.067 mm/mM (0.204 ppm/mM). Following Gd-DTPA administration, patient MR images involving a total of 10 brain metastases/targets were also studied using a similar methodology. Total target localization uncertainty was on average 0.54 mm (2.24 ppm) with the Gd-DTPA induced distortion being of the order of 0.5 mm for the MRI protocol used, in agreement with the phantom study. In an effort to establish what could be considered as acceptable geometric uncertainty, highly conformal plans were utilized to simulate irradiation of targets of different diameters (5 to 50 mm). The targets were deliberately mispositioned by 0.5 up to 3 mm. Dose Volume Histograms (DVHs) and plan quality indices clinically used for plan evaluation and acceptance were derived and used to investigate the effect of geometrical uncertainty (distortion) on dose delivery accuracy and plan quality. The latter was found to be strongly dependent on target size. For targets less than 20 mm in diameter, a spatial displacement of the order of 1 mm could significantly affect (>5%) plan acceptance/quality indices. For targets with diameter greater than 2 cm the corresponding displacement was found greater than 1.5 mm. In the last part of this thesis, distortion correction schemes were developed and/or evaluated. In specific, the efficacy of vendor-supplied distortion correction algorithms (accounting for gradient nonlinearity only) was initially assessed for a variety of scanners, following development of an advanced version of the prototype phantom for high-resolution distortion detection, incorporating nearly 2000 CPs. Moreover, the novel average-image distortion correction methodology was developed and evaluated in both phantom and patient studies. The proposed technique is based on read gradient polarity reversal and, therefore, requires two MR scans. In specific, a new image is created after averaging the signal intensities of corresponding forward and reversed polarity images, on a pixel-by-pixel basis. The method was found efficient for sequence dependent distortion minimization. Furthermore, a comparison study was also conducted involving the more well-established signal integration method. All necessary custom routines were developed in-house. Both distortion correction techniques perform equally well, minimizing the mean and median residual distortions. However, the signal integration method requires a few hours of post-imaging computational time while the average-image method is simple and efficient

Trauma, Tumors, Spine, Functional Neurosurgery

This book is written for graduate students, researchers, and practitioners who are interested in learning how the knowledge from research can be implemented in clinical competences. The first section is dedicated to deep brain stimulation, a surgical procedure which is the paramount example of how clinical practice can take advantage from fundamental research. The second section gathers four chapters on four different topics and illustrates how significant is the challenge to translate scientific advances into clinical practice because the route from evidence to action is not always obvious. It is hoped that this book will stimulate the interest in the process of translating research into practice for a broader range of neurosurgical topics than the one covered by this book, which could result in a forthcoming more comprehensive publication

Computer-Assisted Planning and Robotics in Epilepsy Surgery

Epilepsy is a severe and devastating condition that affects ~1% of the population. Around 30% of these patients are drug-refractory. Epilepsy surgery may provide a cure in selected individuals with drug-resistant focal epilepsy if the epileptogenic zone can be identified and safely resected or ablated. Stereoelectroencephalography (SEEG) is a diagnostic procedure that is performed to aid in the delineation of the seizure onset zone when non-invasive investigations are not sufficiently informative or discordant. Utilizing a multi-modal imaging platform, a novel computer-assisted planning (CAP) algorithm was adapted, applied and clinically validated for optimizing safe SEEG trajectory planning. In an initial retrospective validation study, 13 patients with 116 electrodes were enrolled and safety parameters between automated CAP trajectories and expert manual plans were compared. The automated CAP trajectories returned statistically significant improvements in all of the compared clinical metrics including overall risk score (CAP 0.57 +/- 0.39 (mean +/- SD) and manual 1.00 +/- 0.60, p < 0.001). Assessment of the inter-rater variability revealed there was no difference in external expert surgeon ratings. Both manual and CAP electrodes were rated as feasible in 42.8% (42/98) of cases. CAP was able to provide feasible electrodes in 19.4% (19/98), whereas manual planning was able to generate a feasible electrode in 26.5% (26/98) when the alternative generation method was not feasible. Based on the encouraging results from the retrospective analysis a prospective validation study including an additional 125 electrodes in 13 patients was then undertaken to compare CAP to expert manual plans from two neurosurgeons. The manual plans were performed separately and blindly from the CAP. Computer-generated trajectories were found to carry lower risks scores (absolute difference of 0.04 mm (95% CI = -0.42-0.01), p = 0.04) and were subsequently implanted in all cases without complication. The pipeline has been fully integrated into the clinical service and has now replaced manual SEEG planning at our institution. Further efforts were then focused on the distillation of optimal entry and target points for common SEEG trajectories and applying machine learning methods to develop an active learning algorithm to adapt to individual surgeon preferences. Thirty-two patients were prospectively enrolled in the study. The first 12 patients underwent prospective CAP planning and implantation following the pipeline outlined in the previous study. These patients were used as a training set and all of the 108 electrodes after successful implantation were normalized to atlas space to generate ‘spatial priors’, using a K-Nearest Neighbour (K-NN) classifier. A subsequent test set of 20 patients (210 electrodes) were then used to prospectively validate the spatial priors. From the test set, 78% (123/157) of the implanted trajectories passed through both the entry and target spatial priors defined from the training set. To improve the generalizability of the spatial priors to other neurosurgical centres undertaking SEEG and to take into account the potential for changing institutional practices, an active learning algorithm was implemented. The K-NN classifier was shown to dynamically learn and refine the spatial priors. The progressive refinement of CAP SEEG planning outlined in this and previous studies has culminated in an algorithm that not only optimizes the surgical heuristics and risk scores related to SEEG planning but can also learn from previous experience. Overall, safe and feasible trajectory schema were returning in 30% of the time required for manual SEEG planning. Computer-assisted planning was then applied to optimize laser interstitial thermal therapy (LITT) trajectory planning, which is a minimally invasive alternative to open mesial temporal resections, focal lesion ablation and anterior 2/3 corpus callosotomy. We describe and validate the first CAP algorithm for mesial temporal LITT ablations for epilepsy treatment. Twenty-five patients that had previously undergone LITT ablations at a single institution and with a median follow up of 2 years were included. Trajectory parameters for the CAP algorithm were derived from expert consensus to maximize distance from vasculature and ablation of the amygdalohippocampal complex, minimize collateral damage to adjacent brain structures whilst avoiding transgression of the ventricles and sulci. Trajectory parameters were also optimized to reduce the drilling angle to the skull and overall catheter length. Simulated cavities attributable to the CAP trajectories were calculated using a 5-15 mm ablation diameter. In comparison to manually planned and implemented LITT trajectories,CAP resulted in a significant increase in the percentage ablation of the amygdalohippocampal complex (manual 57.82 +/- 15.05% (mean +/- S.D.) and unablated medial hippocampal head depth (manual 4.45 +/- 1.58 mm (mean +/- S.D.), CAP 1.19 +/- 1.37 (mean +/- S.D.), p = 0.0001). As LITT ablation of the mesial temporal structures is a novel procedure there are no established standards for trajectory planning. A data-driven machine learning approach was, therefore, applied to identify hitherto unknown CAP trajectory parameter combinations. All possible combinations of planning parameters were calculated culminating in 720 unique combinations per patient. Linear regression and random forest machine learning algorithms were trained on half of the data set (3800 trajectories) and tested on the remaining unseen trajectories (3800 trajectories). The linear regression and random forest methods returned good predictive accuracies with both returning Pearson correlations of ρ = 0.7 and root mean squared errors of 0.13 and 0.12 respectively. The machine learning algorithm revealed that the optimal entry points were centred over the junction of the inferior occipital, middle temporal and middle occipital gyri. The optimal target points were anterior and medial translations of the centre of the amygdala. A large multicenter external validation study of 95 patients was then undertaken comparing the manually planned and implemented trajectories, CAP trajectories targeting the centre of the amygdala, the CAP parameters derived from expert consensus and the CAP trajectories utilizing the machine learning derived parameters. Three external blinded expert surgeons were then selected to undertake feasibility ratings and preference rankings of the trajectories. CAP generated trajectories result in a significant improvement in many of the planning metrics, notably the risk score (manual 1.3 +/- 0.1 (mean +/- S.D.), CAP 1.1 +/- 0.2 (mean +/- S.D.), p<0.000) and overall ablation of the amygdala (manual 45.3 +/- 22.2 % (mean +/- S.D.), CAP 64.2 +/- 20 % (mean +/- S.D.), p<0.000). Blinded external feasibility ratings revealed that manual trajectories were less preferable than CAP planned trajectories with an estimated probability of being ranked 4th (lowest) of 0.62. Traditional open corpus callosotomy requires a midline craniotomy, interhemispheric dissection and disconnection of the rostrum, genu and body of the corpus callosum. In cases where drop attacks persist a completion corpus callosotomy to disrupt the remaining fibres in the splenium is then performed. The emergence of LITT technology has raised the possibility of being able to undertake this procedure in a minimally invasive fashion and without the need for a craniotomy using two or three individual trajectories. Early case series have shown LITT anterior two-thirds corpus callosotomy to be safe and efficacious. Whole-brain probabilistic tractography connectomes were generated utilizing 3-Tesla multi-shell imaging data and constrained spherical deconvolution (CSD). Two independent blinded expert neurosurgeons with experience of performing the procedure using LITT then planned the trajectories in each patient following their current clinical practice. Automated trajectories returned a significant reduction in the risk score (manual 1.3 +/- 0.1 (mean +/- S.D.), CAP 1.1 +/- 0.1 (mean +/- S.D.), p<0.000). Finally, we investigate the different methods of surgical implantation for SEEG electrodes. As an initial study, a systematic review and meta-analysis of the literature to date were performed. This revealed a wide variety of implantation methods including traditional frame-based, frameless, robotic and custom-3D printed jigs were being used in clinical practice. Of concern, all comparative reports from institutions that had changed from one implantation method to another, such as following the introduction of robotic systems, did not undertake parallel-group comparisons. This suggests that patients may have been exposed to risks associated with learning curves and potential harms related to the new device until the efficacy was known. A pragmatic randomized control trial of a novel non-CE marked robotic trajectory guidance system (iSYS1) was then devised. Before clinical implantations began a series of pre-clinical investigations utilizing 3D printed phantom heads from previously implanted patients was performed to provide pilot data and also assess the surgical learning curve. The surgeons had comparatively little clinical experience with the new robotic device which replicates the introduction of such novel technologies to clinical practice. The study confirmed that the learning curve with the iSYS1 devices was minimal and the accuracies and workflow were similar to the conventional manual method. The randomized control trial represents the first of its kind for stereotactic neurosurgical procedures. Thirty-two patients were enrolled with 16 patients randomized to the iSYS1 intervention arm and 16 patients to the manual implantation arm. The intervention allocation was concealed from the patients. The surgical and research team could be not blinded. Trial management, independent data monitoring and trial steering committees were convened at four points doing the trial (after every 8 patients implanted). Based on the high level of accuracy required for both methods, the main distinguishing factor would be the time to achieve the alignment to the prespecified trajectory. The primary outcome for comparison, therefore, was the time for individual SEEG electrode implantation. Secondary outcomes included the implantation accuracy derived from the post-operative CT scan, infection, intracranial haemorrhage and neurological deficit rates. Overall, 32 patients (328 electrodes) completed the trial (16 in each intervention arm) and the baseline demographics were broadly similar between the two groups. The time for individual electrode implantation was significantly less with the iSYS1 device (median of 3.36 (95% CI 5.72 to 7.07) than for the PAD group (median of 9.06 minutes (95% CI 8.16 to 10.06), p=0.0001). Target point accuracy was significantly greater with the PAD (median of 1.58 mm (95% CI 1.38 to 1.82) compared to the iSYS1 (median of 1.16 mm (95% CI 1.01 to 1.33), p=0.004). The difference between the target point accuracies are not clinically significant for SEEG but may have implications for procedures such as deep brain stimulation that require higher placement accuracy. All of the electrodes achieved their respective intended anatomical targets. In 12 of 16 patients following robotic implantations, and 10 of 16 following manual PAD implantations a seizure onset zone was identified and resection recommended. The aforementioned systematic review and meta-analysis were updated to include additional studies published during the trial duration. In this context, the iSYS1 device entry and target point accuracies were similar to those reported in other published studies of robotic devices including the ROSA, Neuromate and iSYS1. The PAD accuracies, however, outperformed the previously published results for other frameless stereotaxy methods. In conclusion, the presented studies report the integration and validation of a complex clinical decision support software into the clinical neurosurgical workflow for SEEG planning. The stereotactic planning platform was further refined by integrating machine learning techniques and also extended towards optimisation of LITT trajectories for ablation of mesial temporal structures and corpus callosotomy. The platform was then used to seamlessly integrate with a novel trajectory planning software to effectively and safely guide the implantation of the SEEG electrodes. Through a single-blinded randomised control trial, the ISYS1 device was shown to reduce the time taken for individual electrode insertion. Taken together, this work presents and validates the first fully integrated stereotactic trajectory planning platform that can be used for both SEEG and LITT trajectory planning followed by surgical implantation through the use of a novel trajectory guidance system

A phantom for the study of positional brain shift

Positional brain shift (PBS) is the term given to the displacement of the brain which occurs upon surgical reorientation of the head and presents as one of the many sources of targeting error in high precision neurosurgery. Due to the impracticality of imaging humans in non-standard positions, however, there is currently insufficient information for surgeons to utilize in order to mitigate against PBS in surgical planning. To better characterise PBS, a novel synthetic model (phantom) of the brain-skull system was developed, comprising hydrogel brain (inc. imaging beads) with water filled ventricle cavity, elastomer dural septa, water filled subarachnoid space, and plastic skull. This phantom was validated by simulating the supine to prone PBS event and mechanically tuning the phantom’s hydrogel brain such that the general magnitude of shift (measured through CT imaging) matched that reported in human MRI studies. Using this phantom, brain shift characterisation was performed for a discrete representation of the continuous spectrum of possible positional transitions in neurosurgery. Here, brain shift was measured across eight positional transitions at 44 locations within the brain. Eight novel PBS maps were produced as a result of this study, with mean brain shift ranging between 0.39 and 0.94 mm and the standard deviation of shift within each PBS map ranging between 0.12 and 0.44 mm. The greatest shift was found upon transition from the supine to elevated right decubitus position, with a shift of 2 mm being measured in the left parietal lobe. Importantly, it was found that, a) clinically significant brain shift took place across all transitions and, b) clinically significant variability took place between the brain shift patterns of individual transitions at the local level. Together these findings further highlight the need for the consideration of PBS in surgical planning and strongly suggest that versatile parametric software are likely needed to account for the variable shifting of neurosurgical targets. The developed phantom has allowed for novel insights into an event otherwise difficult to study in humans. With further developments, it is believed that the phantom can be used to study other similarly problematic events, such as trauma