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Radiotherapy is a potential curative option for liver cancer; however, respiratory motion creates uncertainty in treatment delivery. Advances in imaging and registration techniques can provide information regarding changes in respiratory motion. Currently image registration is challenged by computation and manual intervention. A Navigator Channel (NC) technique was developed to overcome these limitations. A population motion model was generated to predict patient-specific motion, while a point motion detection technique was developed to calculate the patient-specific liver edge motion from images. An adaptation technique uses the relative difference between the population and patient calculated liver edge motion to determine the patient's liver volume motion. The NC technique was tested on patient 4D-CT images for initial validation to determine the accuracy. Accuracy was less than 0.10 mm in liver edge detection and approximately 0.25 cm in predicting patient-specific motion. This technique can be used to ensure accurate treatment delivery for liver radiotherapy.

Radiotherapy is a potential curative option for liver cancer; however, respiratory motion creates uncertainty in treatment delivery. Advances in imaging and registration techniques can provide information regarding changes in respiratory motion. Currently image registration is challenged by computation and manual intervention. A Navigator Channel (NC) technique was developed to overcome these limitations. A population motion model was generated to predict patient-specific motion, while a point motion detection technique was developed to calculate the patient-specific liver edge motion from images. An adaptation technique uses the relative difference between the population and patient calculated liver edge motion to determine the patient's liver volume motion. The NC technique was tested on patient 4D-CT images for initial validation to determine the accuracy. Accuracy was less than 0.10 mm in liver edge detection and approximately 0.25 cm in predicting patient-specific motion. This technique can be used to ensure accurate treatment delivery for liver radiotherapy.

Abstract Interactive image-guided neurosurgery for the resection of brain tumors was developed within the last 10 years at different neurosurgical centers around the world to improve the safety of the surgery and the functional outcome of the patients. Since 1987, the Oulu Neuronavigator System, consisting mainly of a mechanical arm, visualization software, an ultrasound transducer and a computer, was developed at the Neurosurgical Research Unit, University of Oulu, Finland. It was the first system to incorporate the principle of the common surgical axis for visualization, including intraoperative ultrasonography. A precommercial version of the device was jointly developed with Elekta Ab, Stockholm, Sweden, as a public project under EUREKA and introduced into a clinical beta-phase trial in 1994 as the Leksell Index System™. A total of 19 operations were performed at the Oulu University Hospital between September 1994 and September 1996 for patients harboring different kinds of intracranial tumors, especially cerebral gliomas. This thesis gives a comprehensive review of the literature from the roots of stereotaxy to the latest developments in interactive image-guided neurosurgery and discusses the advantages and disadvantages of the Leksell Index System™ with special reference to the clinical series that was performed at our institution. Future therapy strategies for the treatment of patients with cerebral gliomas, especially glioblastoma multiforme are envisioned, focusing on the further improvement of surgical interventions. The clinical trial proved that the employed neuronavigator system is versatile and safe and that there are no adverse effects, complications or surgical mortality due to the device. It enabled the surgeon to plan smaller sized and better centered skin incisions and craniotomies and to approach the target lesion with less dissection of intact brain tissue. Despite more radical removal of lesions the overall invasiveness of the operation was decreased in 63.2% of the cases, the duration of the procedure was decreased in 78.9%, and the surgeon's feeling of safety could be improved in 89.5% of the operations. Due to the use of intraoperative imaging (with ultrasound) the experience provides a unique basis for next generation neuronavigators and also for interventional MRI.

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"This dissertation describes the development of a methodology for implementing robotic systems for interventional procedures under intraoperative Magnetic Resonance Imaging (MRI) guidance. MRI is an ideal imaging modality for surgical guidance of diagnostic and therapeutic procedures, thanks to its ability to perform high resolution, real-time, and high soft tissue contrast imaging without ionizing radiation. However, the strong magnetic field and sensitivity to radio frequency signals, as well as tightly confined scanner bore render great challenges to developing robotic systems within MRI environment. Discussed are potential solutions to address engineering topics related to development of MRI-compatible electro-mechanical systems and modeling of steerable needle interventions. A robotic framework is developed based on a modular design approach, supporting varying MRI-guided interventional procedures, with stereotactic neurosurgery and prostate cancer therapy as two driving exemplary applications. A piezoelectrically actuated electro-mechanical system is designed to provide precise needle placement in the bore of the scanner under interactive MRI-guidance, while overcoming the challenges inherent to MRI-guided procedures. This work presents the development of the robotic system in the aspects of requirements definition, clinical work flow development, mechanism optimization, control system design and experimental evaluation. A steerable needle is beneficial for interventional procedures with its capability to produce curved path, avoiding anatomical obstacles or compensating for needle placement errors. Two kinds of steerable needles are discussed, i.e. asymmetric-tip needle and concentric-tube cannula. A novel Gaussian-based ContinUous Rotation and Variable-curvature (CURV) model is proposed to steer asymmetric-tip needle, which enables variable curvature of the needle trajectory with independent control of needle rotation and insertion. While concentric-tube cannula is suitable for clinical applications where a curved trajectory is needed without relying on tissue interaction force. This dissertation addresses fundamental challenges in developing and deploying MRI-compatible robotic systems, and enables the technologies for MRI-guided needle-based interventions. This study applied and evaluated these techniques to a system for prostate biopsy that is currently in clinical trials, developed a neurosurgery robot prototype for interstitial thermal therapy of brain cancer under MRI guidance, and demonstrated needle steering using both asymmetric tip and pre-bent concentric-tube cannula approaches on a testbed."

Needle-based interventions are pervasive in Minimally Invasive Surgery (MIS), and are often used in a number of diagnostic and therapeutic procedures, including biopsy and brachytherapy seed placement. Magnetic Resonance Imaging (MRI) which can provide high quality, real time and high soft tissue contrast imaging, is an ideal guidance tool for image-guided therapy (IGT). Therefore, a MRI-guided needle-based surgical robot proves to have great potential in the application of percutaneous interventions. Presented here is the design of reconfigurable fiducial-integrated modular needle driver for MRI-guided percutaneous interventions. Further, an MRI-compatible hardware control system has been developed and enhanced to drive piezoelectric ultrasonic motors for a previously developed base robot designed to support the modular needle driver. A further contribution is the development of a fiber optic sensing system to detect robot position and joint limits. A transformer printed circuit board (PCB) and an interface board with integrated fiber optic limit sensing have been developed and tested to integrate the robot with the piezoelectric actuator control system designed by AIM Lab for closed loop control of ultrasonic Shinsei motors. A series of experiments were performed to evaluate the feasibility and accuracy of the modular needle driver. Bench top tests were conducted to validate the transformer board, fiber optic limit sensing and interface board in a lab environment. Finally, the whole robot control system was tested inside the MRI room to evaluate its MRI compatibility and stability.

Near-infrared dyes can be used as theranostic agents in cancer management based on their optical imaging and localized hyperthermia capabilities. However, their clinical translatability is limited by issues such as photobleaching, short circulation times, and non-specific biodistribution. We studied the applications of IR820 in optical imaging and hyperthermia, and we prepared nanoconjugate formulations to overcome some of the aforementioned limitations. Free IR820 can be used for optical imaging, with a strong signal still present 24 hours after i.v. injection, an elimination plasma half-life in the order of hours, and primary biodistribution to liver, lung, and kidneys. After 808-mn laser exposure, IR820 can also raise in vitro temperatures to the 41-43°C range that can selectively inhibit cancer cell growth. We conjugated IR820 with PEG-diamine via ionic interactions to create nanoconjugates (IR820-PDNCs) with diameters of approximately 50-nm per SEM and a zeta potential of 2.0±0.9 mV. IR820-PDNCs enhanced cellular internalization compared to IR820 for imaging in SKOV-3, MES-SA, and Dx5 cancer cells. The nanoconjugates also significantly enhanced hyperthermia-mediated cytotoxicity in MES-SA and Dx5 compared to the free dye (p

Image-guided radiation therapy (IGRT) provides accurate and precise tumour targeting. To ensure adequate coverage in IGRT, a planning target volume (PTV) margin is added around the target to account for treatment uncertainties. Treatment plans are designed to deliver a high percentage of the prescription dose to the PTV; thus, portions of healthy tissue are also subjected to high radiation dose. IGRT employs dedicated devices that enable visual assessment of some treatment uncertainties, such as variations in patient set-up. Safe and effective IGRT delivery requires adherence to disease site-specific protocols that describe process details such as imaging technique, alignment method, and corrective action levels. Protocol design is challenging since its effect on treatment accuracy is currently unknown. This thesis aims to understand the interplay between lung IGRT protocol parameters by developing a framework that quantifies geometrical accuracy. Deformable image registration was used to account for changes in target shape and size throughout treatment. Sufficient accuracy was considered when at least 99% of the target surface fell within the PTV. This analysis revealed that the clinical 10 mm PTV margin can be safely reduced by at least 2 mm in each direction. Evaluation of IGRT accuracy was extended to spinal cord alignment. Simulations were carried out with various matching strategies to correct for set-up error, including rotational off-sets. Inappropriate combinations of matching strategies and safety margins resulted in sub-optimal geometrical coverage. Various lung IGRT protocol options were recommended to optimize accuracy and workflow efficiency. For example, an 8 mm PTV margin can be used with spinal cord alignment, a 4 mm cord margin, and up to 5° of rotational error. A more aggressive protocol involved a 6 mm PTV margin with direct target alignment, a 5 mm cord margin, and a 4° rotational tolerance. / Thesis / Master of Science (MSc)

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